FGFR tyrosine kinase inhibitors for the treatment of advanced solid tumors

Abstract

Disclosed herein is a method of treating cancer, the method comprising administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and carrying at least one fibroblast growth factor receptor (FGFR) fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. Also disclosed herein is a method of treating cancer, comprising evaluating a biological sample from a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, the cancer being cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid cancer, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR genetic alteration is present in the sample.

Description

[Technical Field]

[0001] Disclosed herein are methods of treating cancer, the methods comprising administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and carrying at least one fibroblast growth factor receptor (FGFR) fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. Also disclosed herein are methods of treating cancer, the methods comprising administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is an advanced solid tumor, and optionally the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small-cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. [Background technology]

[0002] Identifying genetic abnormalities can be useful in selecting appropriate therapeutic agents for cancer patients. Identifying genetic abnormalities is also useful for cancer patients who have failed the primary treatment option (first-line therapy) for their cancer type, especially when there is no accepted standard of care for second- and subsequent-line therapy. Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases involved in regulating cell survival, proliferation, migration, and differentiation. Alterations in FGFRs can function as oncogenic drivers of disease, regardless of the underlying tumor type. Little is known about the incidence, diversity, or predominant FGFR alterations across solid tumors in the clinical setting. Summary of the Invention [Means for solving the problem]

[0003] Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2.

[0004] In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

[0005] In certain embodiments, the FGFR fusion is FGFR2-CCDC102A. In further embodiments, the cancer is non-squamous NSCLC.

[0006] In certain embodiments, the FGFR fusion is FGFR2-CCDC147. In further embodiments, the FGFR fusion is FGFR2-ENOX1. In even further embodiments, the FGFR fusion is FGFR2-LCN10. In certain embodiments, the FGFR fusion is FGFR2-PDE3A. In further embodiments, the FGFR fusion is FGFR2-RANBP2. In even further embodiments, the FGFR fusion is RRM2B-FGFR2. In certain embodiments, the cancer is cholangiocarcinoma.

[0007] In certain embodiments, the FGFR fusion is FGFR2-GPHN. In further embodiments, the cancer is pancreatic cancer.

[0008] In certain embodiments, the FGFR fusion is FGFR3-ENOX1. In further embodiments, the FGFR fusion is FGFR3-TMEM247. In certain embodiments, the cancer is high-grade glioma.

[0009] In certain embodiments, the FGFR fusion is IGSF3-FGFR1. In further embodiments, the cancer is thymic carcinoma.

[0010] In certain embodiments, the FGFR fusion is RHPN2-FGFR1. In further embodiments, the cancer is ovarian cancer.

[0011] Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0012] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of erdafitinib to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.

[0013] In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0014] In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0015] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR 2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGF R2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, F GFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2- POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FG FGFR3-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0016] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-AMOT, FGFR2-ATAD2, FGFR1-ALPHA, FGFR1-ALPHA- ... FR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1 , FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KI F6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B , FGFR2-PTEN, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TC ERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0017] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMO T, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2- D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR 2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGF R2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D 5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0018] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-CTNND2, FGFR2-YPEL5, FGFR2-SENP6, FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AG AP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57 , FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659 M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2- PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, F GFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0019] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FG FR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR 2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-P OC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGF R2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S 371G, FGFR3-TACC3, FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, FGFR3-P250R, or FGFR3-R399C.

[0020] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ALDH1L1 ... -CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGF R2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, F GFR2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2 -TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR 3-S371G, FGFR3-TACC3, FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, or FGFR3-P250R.

[0021] In some embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NOL4 ... GFR2-PAWR, FGFR2-SENP6, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-TACC3, FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, or FGFR3-S249C.

[0022] In certain embodiments, the subject has received at least one line of systemic therapy prior to administration of said erdafitinib.

[0023] In certain embodiments, the methods or uses described herein further comprise assessing a biological sample from the patient for the presence of at least one FGFR fusion, particularly at least one fusion described herein, or at least one FGFR genetic alteration, particularly at least one genetic alteration described herein, prior to administering said erdafitinib. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof.

[0024] In a further embodiment, erdafitinib is administered daily, specifically once a day. In yet a further embodiment, erdafitinib is administered orally. In certain embodiments, erdafitinib is administered orally every day, specifically once a day.

[0025] In some embodiments, the patient is 15 years of age or older on the first day of administration of the FGFR inhibitor, specifically erdafitinib. In some embodiments, erdafitinib is orally administered daily at a dose of about 8 mg, specifically once a day. In some embodiments, erdafitinib is orally administered daily at a dose of about 9 mg, specifically once a day.

[0026] In some embodiments, the patient is between 12 and 15 years old on the first day of administration of the FGFR inhibitor, specifically erdafitinib. In certain embodiments, erdafitinib is administered orally daily at a dose of about 5 mg, specifically once daily. In some embodiments, erdafitinib is administered orally daily at a dose of about 6 mg, specifically once daily. In some embodiments, erdafitinib is administered orally daily at a dose of about 8 mg, specifically once daily.

[0027] In some embodiments, the patient is between 6 and 12 years old on the first day of administration of the FGFR inhibitor, specifically erdafitinib. In certain embodiments, erdafitinib is administered orally daily at a dose of about 3 mg, specifically once daily. In some embodiments, erdafitinib is administered orally daily at a dose of about 4 mg, specifically once daily. In some embodiments, erdafitinib is administered orally daily at a dose of about 5 mg, specifically once daily.

[0028] In certain embodiments, erdafitinib is administered in a solid dosage form. In further embodiments, the solid dosage form is a tablet.

[0029] Described herein are methods for treating cancer in a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, comprising, consisting of, or consisting essentially of administering a therapeutically effective dose of an FGFR inhibitor to the patient. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN. In one embodiment, the FGFR inhibitor is erdafitinib.

[0030] Described herein are methods of treating cancer comprising, consisting of, or consisting essentially of evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR fusion is present in the sample. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN. In one embodiment, the FGFR inhibitor is erdafitinib.

[0031] Also described herein are methods of treating cancer comprising, consisting of, or consisting essentially of determining whether a patient diagnosed with cancer carries at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, and if the patient carries at least one FGFR fusion, administering a therapeutically effective dose of an FGFR inhibitor to the patient. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. In one embodiment, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN. In one embodiment, the FGFR inhibitor is erdafitinib.

[0032] Also described herein are methods of treating cancer in a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and if at least one FGFR genetic alteration is present in the sample, the method comprises, consists of, or consists essentially of administering to the patient a therapeutically effective dose of an FGFR inhibitor. In one embodiment, the FGFR inhibitor is erdafitinib.

[0033] Also described herein are methods of treating cancer in a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, If the patient has salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal carcinoma, gallbladder carcinoma, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer and at least one FGFR gene alteration is present in the sample, the method comprises, consists of, or consists essentially of administering to the patient a therapeutically effective dose of an FGFR inhibitor. In one embodiment, the FGFR inhibitor is erdafitinib.

[0034] In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0035] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR genetic alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0036] Also described herein is a method of treating cancer, comprising evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR gene alteration, the cancer including, but not limited to, cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, and the like. and administering to the patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR genetic alteration is present in the sample. In one embodiment, the method comprises, consists of, or consists essentially of assessing the patient's tumor to be adenocarcinoma, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal carcinoma, gallbladder carcinoma, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0037] In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0038] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of assessing whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR genetic alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0039] Also described herein is a method of treating cancer, comprising determining whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, including, but not limited to, cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, pre-existing glioma, and / or urothelial cancer. and administering to the patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR genetic alteration is present in the sample that is prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal carcinoma, gallbladder carcinoma, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0040] In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0041] Described herein is an FGFR inhibitor for use in treating cancer in patients harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0042] Described herein is an FGFR inhibitor for use in treating cancer in patients harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

[0043] Described herein is an FGFR inhibitor for use in treating cancer in patients harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, wherein the FGFR inhibitor is selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. The FGFR inhibitor is administered or should be administered if, after evaluating a biological sample from a patient for the presence of at least one FGFR fusion selected from GFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2 is present in the sample. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0044] Described herein is an FGFR inhibitor for use in treating cancer in a patient harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1, wherein the FGFR inhibitor is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. After evaluating a biological sample from a patient for the presence of at least one FGFR fusion selected from FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1, an FGFR inhibitor is administered or should be administered if at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1 is present in the sample. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

[0045] Also described herein is an FGFR inhibitor for use in treating cancer in patients harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0046] Also described herein is an FGFR inhibitor for use in treating cancer in patients harboring at least one FGFR gene alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. The FGFR inhibitor must be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0047] Also described herein is an FGFR inhibitor for use in treating cancer in a patient harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and wherein the FGFR inhibitor is administered or should be administered if at least one FGFR genetic alteration is present in the sample after evaluating a biological sample from the patient for the presence of at least one FGFR genetic alteration. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0048] Also described herein are FGFR inhibitors for use in treating cancer in patients harboring at least one FGFR genetic alteration, including cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, The cancer is thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal carcinoma, gallbladder carcinoma, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer, and the FGFR inhibitor is administered or should be administered if at least one FGFR genetic alteration is present in the sample after evaluating a biological sample from the patient for the presence of at least one FGFR genetic alteration. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0049] Further described herein is the use of an FGFR inhibitor for the manufacture of a medicament for treating a patient diagnosed with cancer and carrying at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0050] Further described herein is the use of an FGFR inhibitor for the manufacture of a medicament for treating a patient diagnosed with cancer and having at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The FGFR inhibitor must be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

[0051] Further described herein is the use of an FGFR inhibitor for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, wherein the FGFR inhibitor is selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. The present invention relates to the use of an FGFR inhibitor, which is administered or should be administered if, after evaluating a biological sample from a patient for the presence of at least one FGFR fusion selected from NBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2 is present in the sample. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0052] Further described herein is the use of an FGFR inhibitor for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1, wherein the FGFR inhibitor is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The present invention relates to the use of an FGFR inhibitor, which is administered or should be administered if at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1 is present in a biological sample from a patient after evaluating the sample for the presence of at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

[0053] Also described herein is the use of an FGFR inhibitor for the manufacture of a medicament for treating a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0054] Also described herein is the use of an FGFR inhibitor for the manufacture of a medicament for treating a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. The FGFR inhibitor must be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0055] Also described herein is the use of an FGFR inhibitor for the manufacture of a medicament for treating a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, wherein the FGFR inhibitor is or should be administered if at least one FGFR genetic alteration is present in the sample after evaluating a biological sample from the patient for the presence of at least one FGFR genetic alteration. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib.

[0056] Also described herein is the use of an FGFR inhibitor for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, including but not limited to cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, and the like. The present invention relates to the use of an FGFR inhibitor in a patient with cancer selected from the group consisting of ovarian cancer, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, and thyroid cancer, and the FGFR inhibitor is administered or should be administered if at least one FGFR genetic alteration is present in a biological sample from the patient after evaluation of the sample for the presence of at least one FGFR genetic alteration. The FGFR inhibitor should be administered at a therapeutically effective dose. In one embodiment, the FGFR inhibitor is erdafitinib. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. [Brief explanation of the drawings]

[0057] The Summary of the Invention, as well as the Detailed Description that follows, will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the methods or uses of the present disclosure, exemplary embodiments of the methods or uses are shown in the drawings. However, the methods or uses are not limited to the particular embodiments disclosed. The drawings are as follows: [Figure 1]Schematic diagram of the clinical study exemplified herein. a) A maximum of 30 subjects per tumor histology will be enrolled in the broad panel cohort. b) Enrollment in the exploratory cohort will be limited to patients with FGFR mutations who do not meet the broad panel cohort molecular eligibility criteria. c) A separate cholangiocarcinoma expansion cohort will enroll subjects with targeted FGFR mutations or any FGFR gene fusions once the broad panel cohort reaches its limit of approximately 30 subjects for cholangiocarcinoma. d) The pediatric cohort will enroll 20 pediatric and adolescent subjects who have progressed after prior therapy and do not have an acceptable standard therapy, and approximately 6 additional pediatric and adolescent subjects newly diagnosed with solid tumors and do not have an acceptable standard therapy. Adolescent subjects (ages 12 to 18 years) enrolled in the broad panel cohort will be analyzed as part of the broad panel cohort and the pediatric cohort. Therefore, the 240 subjects in the broad panel cohort can include subjects from the pediatric cohort. eSubjects with FGFR mutations (excluding valine gatekeeper and resistance alterations), and FGFR gene fusions or FGFR internal tandem duplications are eligible for enrollment in the pediatric cohort. fLists of target FGFR mutations are provided separately in Examples 1A and 1B. [Figure 2] 1 shows indications for erdafitinib dose escalation based on serum phosphorus levels. [Figure 3A] 1 is a pie chart showing primary tumor diagnoses for the molecularly eligible population (N=191) from the clinical study described in Example 2. [Figure 3B] 1 is a pie chart showing primary tumor diagnoses for the enrolled population (N=110) from the clinical study described in Example 2. [Figure 4] Waterfall plot of maximum percent reduction in target lesions from the efficacy analysis population. [Figure 5] Swimlane plot for treatment duration and response, i.e., responders with investigator-confirmed CR / PR. [Figure 6]Waterfall plot of maximum percentage reduction in target lesions from baseline - Independent Radiographic Review (Broad Panel Cohort), treated subjects. CCA = cholangiocarcinoma; HGG = high-grade glioma; BRST = breast cancer; PANCR = pancreatic cancer; sqNSCLC = squamous NSCLC; nonsqNSCLC = non-squamous NSCLC; CRC = colorectal cancer; EDMTL = endometrial cancer; ESOPH = esophageal cancer; LGG = low-grade glioma; GSTRC = gastric cancer; HNSCC = squamous head and neck cancer; CRVX = cervical cancer; OVAR = ovarian cancer; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; NE: not evaluable. The best overall response is the best response recorded from the start of study treatment to the end of the study, taking into account any requirement for confirmation, before PD and subsequent anticancer therapy (subsequent surgery / procedure, subsequent radiation therapy, and subsequent systemic treatment). For disease assessment based on RECIST 1.1, the maximum percent reduction from baseline is calculated in the sum of target lesion diameters. For disease assessment based on RANO, the maximum percent reduction from baseline is calculated in the sum of the products of the perpendicular dimensions. A maximum increase in target lesions from baseline greater than 100% is set to 100%. At the time of data cut, one subject had an "unknown" FGFR mutation / fusion. The subject's FGFR status has since been confirmed as an FGFR fusion. [Figure 7] Swimlane plot of treatment duration and response - Independent radiographic review (broad panel cohort), IRC-confirmed responders with CR / PR. CCA = cholangiocarcinoma; HGG = high-grade glioma; BRST = breast cancer; PANCR = pancreatic cancer; sqNSCLC = squamous NSCLC; nonsqNSCLC = non-squamous NSCLC; EDMTL = endometrial cancer; ESOPH = esophageal cancer; LGG = low-grade glioma; HNSCC = squamous head and neck cancer; OVAR = ovarian cancer. * indicates patient is still on treatment. + indicates response duration is currently censored for patient. [Figure 8]Forest plot of objective response rate by subgroup - independent radiographic review (broad panel cohort), treated subjects. CR: complete response; PR: partial response. DETAILED DESCRIPTION OF THE INVENTION

[0058] It is understood that certain features of the invention that are described herein for clarity in the context of separate embodiments may also be provided in combination in a single embodiment. That is, unless expressly incompatible or specifically excluded, each individual embodiment is deemed combinable with any other embodiment, and such combinations are deemed to be separate embodiments. Conversely, different features of the invention that are described for brevity in the context of a single embodiment may also be provided separately or in any subcombination. Finally, while embodiments may be described as part of a series of steps or as part of a more general structure, each step thereof may be deemed to be an independent embodiment in itself, combinable with the others.

[0059] Specific Terms The transitional phrases "comprising," "consisting essentially of," and "consisting" are intended to connote their generally accepted meanings in patent terminology, i.e., (i) "comprising" is synonymous with "including," "containing," or "characterized by" and is inclusive or open-ended and does not exclude other unrecited elements or method steps; (ii) "consisting" excludes any element, step, or ingredient not specified in the claim; and (iii) "consisting essentially of" limits the scope of a claim or embodiment to the specified materials or steps and those that "do not materially affect the basic and novel characteristics" of the claimed invention or embodiment. More specifically, the basic and novel characteristics relate to the ability of the method or use to provide at least one of the benefits described herein, including, but not limited to, improved survival of a human population compared to survival of a human comparison population, as described elsewhere herein. Embodiments described with the term "comprising" (or its equivalents) also provide, as embodiments, those independently described with the terms "consisting of" and "consisting essentially of."

[0060] When values ​​are expressed as approximations, by use of the descriptor "about," it will be understood that the particular value forms another embodiment. Unless otherwise specified, the term "about" means a variation of ±10% of the associated value, although further embodiments include those where the variation can be ±5%, ±15%, ±20%, ±25%, or ±50%, and specifically, the term "about" means a variation of ±5% or ±10%, more specifically ±5% of the associated value.

[0061] When lists are presented, it is to be understood that each individual element of that list and every combination of that list is a separate embodiment, unless otherwise specified. For example, a list of embodiments presented as "A, B, or C" should be interpreted to include the embodiments "A," "B," "C," "A or B," "A or C," "B or C," or "A, B, or C."

[0062] As used herein, the singular forms "a," "an," and "the" are intended to include plurals.

[0063] As used herein, a "patient" is intended to mean any animal, particularly a mammal. Thus, the present method or use is applicable to human and non-human animals, but most preferably to humans. The terms "patient" and "subject" can be used interchangeably.

[0064] The terms "treat" and "treatment" refer to the treatment of a patient affected by a pathological condition, and refer not only to alleviating the condition by killing cancer cells, but also to inhibiting the progression of the condition, including slowing the rate of progression, stopping the rate of progression, ameliorating the condition, and curing the condition. Preventative treatment (i.e., prophylaxis) is also included.

[0065] A "therapeutically effective amount" refers to an amount effective to obtain a desired therapeutic result, at dosages and for periods of time necessary. A therapeutically effective amount may vary depending on factors such as the individual's disease state, age, sex, and weight, as well as the ability of the therapeutic agent or combination of therapeutic agents to elicit a desired response in the individual. Exemplary indicators of an effective therapeutic agent or combination of therapeutic agents include, for example, improved health of the patient.

[0066] "Dosage" refers to information regarding the amount of a therapeutic agent taken by a subject and the frequency with which the therapeutic agent is taken by a subject.

[0067] The term "dose" refers to the amount or quantity of a therapeutic agent taken at each time.

[0068] As used herein, the term "cancer" refers to an abnormal growth of cells that tends to grow without control and in some cases to invade (spread).

[0069] The term "continuous daily dosing schedule" refers to the administration of a particular therapeutic agent without any drug holidays for that particular therapeutic agent. In some embodiments, a continuous daily dosing schedule for a particular therapeutic agent comprises administering the particular therapeutic agent every day at approximately the same time each day.

[0070] As used herein, the term "co-administration" and the like is intended to encompass the administration of selected therapeutic agents to a single patient and includes therapeutic regimens in which the agents are administered by the same or different routes of administration or at the same or different times.

[0071] The term "adverse event" is any untoward medical occurrence in a clinical trial subject administered a medicinal product (investigational or non-investigational). An adverse event does not necessarily have a causal relationship to the intervention. Thus, an adverse event can be any untoward, unintended sign (e.g., an abnormal laboratory test result), symptom, or disease that is temporally related to the use of a medicinal product (investigational or non-investigational), whether or not it has a causal relationship to the medicinal product (investigational or non-investigational).

[0072] As used herein, the term "placebo" refers to the administration of a pharmaceutical composition that does not contain an FGFR inhibitor.

[0073] The term "randomization," when applied to a clinical trial, refers to the point at which patients are identified as eligible for the clinical trial and assigned to a treatment group.

[0074] The terms "kit" and "article of manufacture" are used synonymously.

[0075] The terms "objective response rate" and "overall response rate" are used interchangeably herein.

[0076] "Biological sample" refers to any sample obtained from a patient from which cancerous cells can be obtained and from which FGFR gene alterations can be detected. Suitable biological samples include, but are not limited to, blood, lymph, bone marrow, solid tumor samples, or any combination thereof. In some embodiments, the biological sample may be formalin-fixed paraffin-embedded tissue (FFPET).

[0077] In the context of determining whether a patient has at least one FGFR gene alteration, the term "determining" includes a medical professional reviewing the results (or results) of the biological sample evaluation for the presence of one or more FGFR gene alterations.For example, based on reviewing such results (e.g., patient sequencing results by next-generation sequencing, direct sequencing, etc.), a medical professional may determine (recognize) that the patient has at least one FGFR gene alteration, such as the fusion (or fusions) described herein.Based on this determination, according to certain embodiments, administering erdafitinib becomes part of the patient's treatment regimen.

[0078] The term "intact FGFR kinase domain" refers to (a) an FGFR fusion with a 3-prime partner (the FGFR gene is listed first, e.g., FGFR-GENE or FGFR3-TACC3), where the FGFR portion of the fusion must include exon 17 or greater; (b) an FGFR fusion with a 5-prime partner (the partner gene is listed first and the FGFR gene is second, e.g., GENE-FGFR), where the FGFR portion of the fusion must include exon 11 or less; or (c) a named FGFR fusion partner gene (self-fusions or rearrangements, e.g., FGFR-FGFR, are not eligible).

[0079] FGFR gene alterations Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2.

[0080] Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1.

[0081] Described herein are methods of treating cancer, the methods including administering to a patient diagnosed with cancer and a patient selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102, and the like. A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGF R2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B , FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FG FR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1 , FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, FGFR3-P250R,or FGFR3-R399C, or FGFR3-R399C, comprising, consisting of, or consisting essentially of, administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient carrying at least one FGFR genetic alteration selected from

[0082] Described herein are methods of treating cancer, the methods including administering to a patient diagnosed with cancer and expressing one or more of the following: FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NOL4, FGFR2-PAWR, FGFR2-SENP6, FGFR2-TACC2, FGFR2-T The method comprises, consists of, or consists essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient carrying at least one FGFR genetic alteration selected from BC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-TACC3, FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, or FGFR3-S249C.

[0083] In certain embodiments, the patient does not possess a FGFR valine gatekeeper or resistance alteration, specifically a valine gatekeeper or resistance alteration selected from FGFR1 V561, FGFR2 V564, FGFR3 V555, FGFR4 V550, FGFR1 N546, FGFR2 N549, FGFR3 N540, and FGFR4 N535.

[0084] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, where the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0085] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, and cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), and non-squamous NSCLC. In certain embodiments, the cancer is selected from the group consisting of CLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal gland carcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, and thyroid cancer. In certain embodiments, the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, and thyroid cancer.

[0086] In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain. In certain embodiments, the FGFR fusion is an FGFR1 fusion, specifically an FGFR1 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR2 fusion, specifically an FGFR2 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR3 fusion, specifically an FGFR3 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion, specifically an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR2 fusion or an FGFR3 fusion, specifically an FGFR2 fusion or an FGFR3 fusion described herein. In certain embodiments, the FGFR mutation is an FGFR2 mutation, specifically an FGFR2 mutation described herein. In certain embodiments, the FGFR mutation is an FGFR3 mutation, specifically an FGFR3 mutation described herein. In certain embodiments, the FGFR mutation is an FGFR2 mutation or an FGFR3 mutation, specifically an FGFR2 mutation or an FGFR3 mutation described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR1 fusion, specifically an FGFR1 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR2 fusion, specifically an FGFR2 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR3 fusion, specifically an FGFR3 fusion described herein. In certain embodiments, the indication is an advanced solid tumor having an FGFR1, FGFR2, or FGFR3 fusion, particularly an FGFR1, FGFR2, or FGFR3 fusion described herein. In certain embodiments, the indication is an advanced solid tumor having an FGFR2 or FGFR3 fusion, particularly an FGFR2 or FGFR3 fusion described herein.In certain embodiments, the indication is an advanced solid tumor with an FGFR2 mutation, particularly an FGFR2 mutation described herein. In certain embodiments, the indication is an advanced solid tumor with an FGFR3 mutation, particularly an FGFR3 mutation described herein. In certain embodiments, the indication is an advanced solid tumor with an FGFR2 mutation or an FGFR3 mutation, particularly an FGFR2 mutation or an FGFR3 mutation described herein.

[0087] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a pediatric patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is glioblastoma multiforme, low-grade glioma, pilocytic astrocytoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, Ewing's sarcoma, or medulloblastoma. Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a pediatric patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is dysembryonic neuroepithelial tumor, glioblastoma, glioma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, Ewing's sarcoma, or medulloblastoma. In certain embodiments, the glioma includes low-grade glioma and high-grade glioma. In certain embodiments, low-grade glioma includes pilocytic astrocytoma, astrocytoma, piloidoid astrocytoma, oligoastrocytoma, and pleomorphic xanthoastrocytoma. In certain embodiments, high-grade glioma includes anaplastic astrocytoma. In certain embodiments, the patient is 6 years of age or older but younger than 18 years of age. In certain embodiments, the patient is 6 to under 12 years of age. In certain embodiments, the patient is 12 to under 15 years of age. In certain embodiments, the patient is 15 to under 18 years of age. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0088] Also described herein are methods of treating glioblastoma multiforme, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a pediatric patient diagnosed with glioblastoma multiforme and harboring at least one FGFR genetic alteration. In certain embodiments, the patient is 6 to 18 years of age. In certain embodiments, the patient is 6 to 12 years of age. In certain embodiments, the patient is 12 to 15 years of age. In certain embodiments, the patient is 15 to 18 years of age. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain. The fibroblast growth factor (FGF) family of protein tyrosine kinase (PTK) receptors regulates a wide variety of physiological functions, including mitogenesis, wound healing, cell differentiation and angiogenesis, and development. The growth and proliferation of normal and malignant cells are influenced by changes in the local concentration of FGFs, extracellular signaling molecules that act as autocrine and paracrine factors. Autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.

[0089] FGFs and their receptors are expressed at high levels in several tissues and cell lines, and their overexpression is thought to contribute to the malignant phenotype. Furthermore, many oncogenes are homologs of genes encoding growth factor receptors, which may aberrantly activate FGF-dependent signaling in human pancreatic cancer (Knight et al., Pharmacology and Therapeutics 2010 125:1(105-117); Korc M. et al. Current Cancer Drug Targets 2009 9:5(639-651)).

[0090] Acidic fibroblast growth factor (aFGF or FGF1) and basic fibroblast growth factor (bFGF or FGF2) are the two prototypic members, and at least 20 different FGF family members have been identified to date. Cellular responses to FGFs are mediated through four high-affinity transmembrane protein tyrosine kinase fibroblast growth factor receptors (FGFRs), numbered 1 to 4 (FGFR1 to FGFR4).

[0091] In certain embodiments, the cancer is susceptible to FGFR genetic alterations.

[0092] As used herein, "FGFR gene alteration" refers to an alteration in a wild-type FGFR gene, including, but not limited to, an FGFR fusion gene, an FGFR mutation, or any combination thereof. The terms "mutant" and "alteration" are used interchangeably herein.

[0093] In certain embodiments, the FGFR gene alteration is an FGFR gene fusion. "FGFR fusion" or "FGFR gene fusion" refers to a gene encoding a portion of an FGFR (e.g., FGRF2 or FGFR3) and one or a portion of one of the fusion partners disclosed herein, which is created by a translocation between two genes. The terms "fusion" and "translocation" are used interchangeably herein. Tables 9, 14, and 19 provide FGFR fusion genes and FGFRs and fusion partners.

[0094] Table 1 provides a list of exemplary FGFR fusions and gene breakpoints.

[0095] [Table 1]

[0096] In any of the described embodiments, the FGFR fusion can be any FGFR fusion in which the FGFR protein has an intact FGFR kinase domain. In certain embodiments, the at least one FGFR fusion is selected from the group consisting of FGFR1-PLAG1, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-F ... The gene is selected from GFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-TACC3, FGFR3-TMEM247, and FGFR3-WHSC1.

[0097] In certain embodiments, the at least one FGFR fusion is selected from the group consisting of FGFR1-BAG4, IGSF3-FGFR1, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FG FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-PTEN, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-WAC, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-TACC3, FGFR3-TMEM247, and FGFR3-WHSC1.

[0098] In certain embodiments, the at least one FGFR fusion is selected from the group consisting of FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-CTNND2, FGFR2-YPEL5, FGFR2-SENP6, FGFR1-PLAG1, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-E NOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-SYNPO 2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-TACC3, FGFR3-TMEM247, and FGFR3-WHSC1.

[0099] In certain embodiments, the at least one FGFR fusion is selected from the group consisting of BAG4-FGFR1, CD44-FGFR2, FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A , FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-CTNND2, FGFR2-ENOX1, FGFR2-FAM24B, F GFR2-FKBP15, FGFR2-GKAP1, FGFR2-GOLGA2, FGFR2-GPHN, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-KCTD1, FGFR 2-KIAA1598, FGFR2-KIF6, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-PO C1B, FGFR2-SENP6, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2- TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR2-YPEL5, FGFR3-ENOX1, FGFR3-JAKMIP1, FGFR3-MYH14, FGFR3-TACC3, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, WDR11-FGFR2, WHSC1-FGFR3, and WHSC1L1-FGFR1.

[0100] In certain embodiments, the at least one FGFR fusion is selected from FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NOL4, FGFR2-PAWR, FGFR2-SENP6, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, and FGFR3-TACC3.

[0101] In certain embodiments, the at least one FGFR fusion is selected from FFGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2.

[0102] In certain embodiments, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1.

[0103] FGFR genetic alterations include FGFR single nucleotide polymorphisms (SNPs). An "FGFR single nucleotide polymorphism" (SNP) refers to an FGFR gene that differs between individuals by a single nucleotide. In certain embodiments, the FGFR genetic alteration is an FGFR3 genetic mutation. Specifically, an "FGFR single nucleotide polymorphism" (SNP) refers to an FGFR1, FGFR2, or FGFR3 gene that differs between individuals by a single nucleotide. The presence of one or more of the FGFR SNPs in Table 9, Table 14, or Table 19 in a biological sample from a patient can be determined by methods known to those of skill in the art or by the methods disclosed in WO 2016 / 048833.

[0104] In certain embodiments, the at least one FGFR mutation is selected from FGFR1-K656E, FGFR2-C382R, FGFR2-D101Y, FGFR2-F276C, FGFR2-K659M, FGFR2-L551F, FGFR2-L770V, FGFR2-S252L, FGFR2-S267P, FGFR2-V395D, FGFR2-Y375C, FGFR3-A500T, FGFR3-F384L, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, and FGFR3-S371G.

[0105] In certain embodiments, the at least one FGFR mutation is selected from FGFR1-K656E, FGFR2-C382R, FGFR2-D101Y, FGFR2-F276C, FGFR2-K659M, FGFR2-L551F, FGFR2-L770V, FGFR2-S252L, FGFR2-S267P, FGFR2-V395D, FGFR2-Y375C, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, and FGFR3-S371G.

[0106] In certain embodiments, the at least one FGFR mutation is selected from the group consisting of FGFR1-K656E, FGFR1-S125L, FGFR2-C382R, FGFR2-D101Y, FGFR2-E565A, FGFR2-F276C, FGFR2-K659M, FGFR2-L551F, FGFR2-L770V, FGFR2-P253L, FGFR2-S2 52L, FGFR2-S267P, FGFR2-V395D, FGFR2-W72C, FGFR2-Y375C, FGFR3-A500T, FGFR3-F384L, FGFR3-P250R, FGFR3-R248C, FGFR3-R399C, FGFR3-S249C, FGFR3-S249F, and FGFR3-S371G.

[0107] In certain embodiments, the at least one FGFR mutation is selected from FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, and FGFR3-S249C.

[0108] In certain embodiments, the at least one FGFR mutation is not an FGFR valine gatekeeper or resistance alteration, hi certain embodiments, the at least one FGFR mutation is not FGFR1 V561, FGFR2 V564, FGFR3 V555, FGFR4 V550, FGFR1 N546, FGFR2 N549, FGFR3 N540, or FGFR4 N535.

[0109] As used herein, an "FGFR gene alteration gene panel" includes one or more of the FGFR gene alterations listed above. In some embodiments, the FGFR gene alteration gene panel depends on the type of cancer of the patient.

[0110] The FGFR genetic alteration gene panel used in the evaluation step of the disclosed methods is based in part on the patient's type of cancer. For cancer patients, a suitable FGFR genetic alteration gene panel may include any of the FGFR genetic alterations disclosed in Table 9, Table 14, or Table 19. In one embodiment, for cancer patients, a suitable FGFR genetic alteration gene panel may include any of the FGFR genetic alterations disclosed in the target FGFR mutations of Example 1A. In one embodiment, for cancer patients, a suitable FGFR genetic alteration gene panel may include any of the FGFR genetic alterations disclosed in the target FGFR mutations of Example 1B.

[0111] FGFR inhibitors for use in the disclosed methods or uses Provided herein are FGFR inhibitors suitable for use in the disclosed methods or uses. The FGFR inhibitors may be used alone or in combination for the treatment methods described herein.

[0112] In some embodiments, if one or more FGFR genetic alterations are present in the sample, the cancer can be treated with an FGFR inhibitor disclosed in U.S. Patent Application Publication No. 2013 / 0072457(A1), which is incorporated herein by reference, including any tautomers or stereochemical isomers thereof, and N-oxides thereof, pharmaceutically acceptable salts thereof, or solvates thereof.

[0113] In some aspects, for example, cancer can be treated with N-(3,5-dimethoxy-phenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine (referred to herein as "JNJ-42756493" or "JNJ493" or erdafitinib), including any tautomeric form thereof, its N-oxide, its pharmaceutically acceptable salt, or its solvate. In some embodiments, the FGFR inhibitor is a compound of Formula (I), also referred to as erdafitinib:

[0114] [ka] or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutically acceptable salt is an HCl salt. In preferred embodiments, erdafitinib base is used.

[0115] Erdafitinib (also known as ERDA), an oral pan-FGFR kinase inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally advanced UC or mUC harboring sensitive FGFR3 or FGFR2 genetic alterations who have progressed during or after at least one line of prior platinum-containing chemotherapy (including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy). Loriot Y et al., NEJM. 2019;381:338-48. Erdafitinib has demonstrated clinical efficacy and tolerability in patients with mUC and FGFR expression alterations. Tabernero J,et al.,J Clin Oncol.2015;33:3401-3408;Soria JC,et al.,Ann Oncol.2016;27(Suppl 6):vi266-vi295.Abstract 781PD;Siefker-Radtke AO,et al.,ASCO 2018.Abstract 4503;Siefker-Radtke A,et al.,ASCO-GU 2018.Abstract 450.

[0116] In some embodiments, the cancer can be treated with an FGFR inhibitor, wherein the FGFR inhibitor is N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide (AZD4547), as described in Gavine, P.R., et al., AZD4547: An Orally Bioavailable, Potent, and Selective Inhibitor of the Fibroblast Growth Factor Receptor Tyrosine Kinase Family, Cancer Res. April 15, 2012 72;2045.

[0117] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0118] In some embodiments, the cancer can be treated with an FGFR inhibitor, wherein the FGFR inhibitor is 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-l-{6-[4-(4-ethyl-piperazin-l-yl)-phenylamino]-pyrimid-4-yl}-methyl-urea (also known as NVP-BGJ398 or infigratinib), as described in WO 2006 / 000420.

[0119] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0120] In some embodiments, the cancer can be treated with an FGFR inhibitor, wherein the FGFR inhibitor is 4-amino-5-fluoro-3-[6-(4-methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-quinolin-2-one (also known as dovitinib), as described in WO 2006 / 127926.

[0121] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0122] In some embodiments, the cancer can be treated with an FGFR inhibitor, wherein the FGFR inhibitor is 6-(7-((1-aminocyclopropyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) (also known as lusitanib; E-3810), as described in Bello, E. et al., E-3810 Is a Potent Dual Inhibitor of VEGFR and FGFR that Exerts Antitumor Activity in Multiple Preclinical Models, Cancer Res February 15, 2011 71(A)1396-1405 and WO 2008 / 112408.

[0123] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0124] In some embodiments, the cancer can be treated with an FGFR inhibitor, such as (4-{[4-amino-6-(methoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]methyl}piperazin-2-one) (also known as BAY1163877 or rogaratinib), as described in Grunewald et al., Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models, Int Journal of Cancer 145(5), 2019.

[0125] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0126] In some embodiments, the cancer can be treated with an FGFR inhibitor, such as (1-[(3S)-[4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one) (also known as TAS-120 or futibatinib), as described in Sootome et al., Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors, Cancer Res; 80(22) November 15, 2020.

[0127] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0128] In some embodiments, the cancer can be treated with an FGFR inhibitor, and the FGFR inhibitor is 3-(2,6-difluoro-3,5-dimethoxyphenyl)1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3',2':5,6]pyrido[4,3d]pyrimidin-2-one (also known as pemigatinib or Pemazyre®).

[0129] [ka] However, where chemically possible, it includes any tautomers or stereochemical isomers thereof, as well as its N-oxides, its pharmaceutically acceptable salts, or its solvates.

[0130] Further suitable FGFR inhibitors include BAY1179470 (Bayer), ARQ087 (ArQule), ASP5878 (Astellas), FF284 (Chugai), FP-1039 (GSK / FivePrime), Blueprint, LY-2874455 (Lilly), RG-7444 (Roche), or any combination thereof, including, where chemically possible, any tautomers or stereochemical isomers thereof, and N-oxides thereof, pharmaceutically acceptable salts thereof, or solvates thereof.

[0131] In one embodiment, the FGFR inhibitor, more specifically erdafitinib, is generally administered as a pharmaceutically acceptable salt. In a preferred embodiment, the FGFR inhibitor, more specifically erdafitinib, is generally administered in base form. In one embodiment, the FGFR inhibitor, more specifically erdafitinib, is generally administered as a pharmaceutically acceptable salt in an amount equivalent to 5 mg of base equivalent, 6 mg of base equivalent, 8 mg of base equivalent, or 9 mg of base equivalent. In one embodiment, the FGFR inhibitor, more specifically erdafitinib, is generally administered in base form in an amount of 5 mg, 6 mg, 8 mg, or 9 mg. In one embodiment, the FGFR inhibitor, more specifically erdafitinib, is generally administered as a pharmaceutically acceptable salt in an amount equivalent to 3 mg of base equivalent or 4 mg of base equivalent. In one embodiment, generally the FGFR inhibitor, more specifically erdafitinib, is administered in base form in an amount of 3 mg or 4 mg.

[0132] These salts can be prepared, for example, by reacting an FGFR inhibitor in general, and more specifically erdafitinib, with a suitable acid in a suitable solvent.

[0133] Acid addition salts may be formed with both inorganic and organic acids. Examples of acid addition salts include salts formed with acids selected from the group consisting of acetic acid, hydrochloric acid, hydroiodic acid, phosphoric acid, nitric acid, sulfuric acid, citric acid, lactic acid, succinic acid, maleic acid, malic acid, isethionic acid, fumaric acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid (mesylate), ethanesulfonic acid, naphthalenesulfonic acid, valeric acid, acetic acid, propanoic acid, butanoic acid, malonic acid, glucuronic acid, and lactobionic acid. Another group of acid addition salts includes salts formed with acetic acid, adipic acid, ascorbic acid, aspartic acid, citric acid, DL-lactic acid, fumaric acid, gluconic acid, glucuronic acid, hippuric acid, hydrochloric acid, glutamic acid, DL-malic acid, methanesulfonic acid, sebacic acid, stearic acid, succinic acid, and tartaric acid.

[0134] In one embodiment, generally, FGFR inhibitors, more specifically, erdafitinib, are administered in the form of a solvate. As used herein, the term "solvate" refers to the physical association of erdafitinib with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, such as hydrogen bonding. In certain cases, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate can be isolated. The term "solvate" encompasses both solution-phase solvates and isolable solvates. Non-limiting examples of solvents that can form solvates include water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, or ethanolamine.

[0135] Solvates are well known in pharmaceutical chemistry. Solvates can be important in processes for preparing substances (e.g., in connection with their purification), for storage of substances (e.g., their stability), and for ease of handling, and are often formed as part of an isolation or purification step in a chemical synthesis. Those skilled in the art can determine whether hydrates or other solvates are formed by the isolation or purification conditions used to prepare a given compound using standard and long-established techniques. Examples of such techniques include thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray crystallography (e.g., single-crystal X-ray crystallography or X-ray powder diffraction), and solid-state NMR (Solid-State NMR, SS-NMR, also known as Magic Angle Spinning NMR or Magic Angle Spinning NMR, MAS-NMR). These techniques, along with NMR, IR, HPLC, and MS, are part of the standard analytical toolkit of a skilled chemist. Alternatively, one skilled in the art can intentionally form a solvate using crystallization conditions that include the amount of solvent required for the particular solvate. The standard methods described above can then be used to determine whether a solvate has formed. Also included are any complexes (e.g., inclusion complexes or clathrates with compounds such as cyclodextrins, or complexes with metals).

[0136] Additionally, the compounds may have one or more polymorphic (crystalline) or amorphous forms.

[0137] Compounds include compounds with one or more isotopic substitutions, and a reference to a particular element includes within its scope all isotopes of that element. For example, a reference to hydrogen includes within its scope 1 H, 2 H(D), and 3 Similarly, references to carbon and oxygen include within their scope 12 C. 13 C and 14 C, and 16 O and18 Each of the compounds includes O. Such isotopes may be radioactive or non-radioactive isotopes. In one embodiment, the compound does not contain a radioisotope. Such compounds are preferred for therapeutic use. However, in another embodiment, the compound may contain one or more radioisotopes. Compounds containing such radioisotopes may be useful in diagnostic situations.

[0138] Treatment and Use

[0010] Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. In certain embodiments, the cancer is NSCLC, specifically non-squamous NSCLC, cholangiocarcinoma, pancreatic cancer, high-grade glioma, thymic carcinoma, or ovarian cancer.

[0139] Described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. In certain embodiments, the cancer is non-squamous NSCLC, cholangiocarcinoma, pancreatic cancer, high-grade glioma, thymic carcinoma, or ovarian cancer.

[0140] Described herein are methods for treating NSCLC, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient diagnosed with NSCLC, particularly non-squamous NSCLC, and harboring at least one FGFR fusion. In certain embodiments, the at least one FGFR fusion is FGFR2-CCDC102A.

[0141] Described herein is a method for treating cholangiocarcinoma, the method comprising, consisting of, or essentially consisting of administering a therapeutically effective amount of an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cholangiocarcinoma and carrying at least one FGFR fusion. In certain embodiments, at least one FGFR fusion is FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, or RRM2B-FGFR2. In certain embodiments, at least one FGFR fusion is FGFR2-ENOX1 or FGFR2-PDE3A.

[0142] Described herein are methods for treating pancreatic cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with pancreatic cancer and carrying at least one FGFR fusion. In certain embodiments, the FGFR fusion is FGFR2-GPHN.

[0143] Described herein are methods for treating high-grade glioma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with high-grade glioma and harboring at least one FGFR fusion. In certain embodiments, the FGFR fusion is FGFR3-ENOX1.

[0144] Described herein are methods for treating thymic carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with thymic carcinoma and harboring at least one FGFR fusion. In certain embodiments, the FGFR fusion is IGSF3-FGFR1.

[0145] Described herein are methods for treating ovarian cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with ovarian cancer and carrying at least one FGFR fusion. In certain embodiments, the FGFR fusion is RHPN2-FGFR1.

[0146] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0147] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous cell carcinoma, and cholangiocarcinoma. The method is wherein the cancer is NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary cancer, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.

[0148] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, carcinoma of unknown primary, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0149] In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion.

[0150] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with an advanced solid tumor, harboring a targeted FGFR mutation or fusion, who has progressed on or after at least one line of systemic therapy and has no remaining treatment options with established clinical benefit. In certain embodiments, the patient has failed to tolerate standard therapy for the underlying tumor type. In one embodiment, the target FGFR mutation or fusion is as described in one embodiment herein. In one embodiment, the target FGFR mutation or fusion is an FGFR mutation selected from the target FGFR mutations of Example 1A or the target FGFR mutations of Example 1B. In one embodiment, the target FGFR mutation or fusion is an FGFR fusion with an intact FGFR kinase domain. In one embodiment, the target FGFR mutation or fusion is an FGFR mutation selected from the target FGFR mutations of Example 1A or the target FGFR mutations of Example 1B, or an FGFR fusion selected from an FGFR fusion with an intact FGFR kinase domain. In one embodiment, the FGFR inhibitor is erdafitinib.

[0151] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0152] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous cell carcinoma, and cholangiocarcinoma. In certain embodiments, the cancer is selected from the group consisting of NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal gland carcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, and thyroid cancer. In certain embodiments, the cancer is selected from the group consisting of bile duct cancer, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, and thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0153] In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion. In one embodiment, the at least one FGFR genetic alteration, the at least one FGFR mutation, or the at least one FGFR fusion is as described in one embodiment herein. In one embodiment, the at least one FGFR genetic alteration is selected from the target FGFR mutations of Example 1A or selected from the target FGFR mutations of Example 1B. In one embodiment, the at least one FGFR genetic alteration is an FGFR fusion with an intact FGFR kinase domain. In one embodiment, the at least one FGFR genetic alteration is selected from the target FGFR mutations of Example 1A or selected from the target FGFR mutations of Example 1B, or selected from an FGFR fusion with an intact FGFR kinase domain. In one embodiment, the FGFR inhibitor is erdafitinib.

[0154] Also described herein are methods for treating cholangiocarcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cholangiocarcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-AHCYL1, FGFR2-AMOT, FGFR2-BICC1, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-ENOX1, FGFR2-KIAA1598, FGFR2-LGSN, FGFR2-NOL4, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-WAC, and FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-ENOX1, FGFR2-KIAA1598, FGFR2-LGSN, FGFR2-NOL4, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-WAC, and FGFR3-TACC3. In one embodiment, the at least one FGFR fusion is FGFR2-AHCYL1. In one embodiment, the at least one FGFR fusion is FGFR2-AMOT. In one embodiment, the at least one FGFR fusion is FGFR2-BICC1. In one embodiment, the at least one FGFR fusion is FGFR2-CD2AP. In one embodiment, at least one FGFR fusion is FGFR2-CFAP57. In one embodiment, at least one FGFR fusion is FGFR2-ENOX1. In one embodiment, at least one FGFR fusion is FGFR2-KIAA1598. In one embodiment, at least one FGFR fusion is FGFR2-LGSN.In one embodiment, at least one FGFR fusion is FGFR2-NOL4. In one embodiment, at least one FGFR fusion is FGFR2-PAWR. In one embodiment, at least one FGFR fusion is FGFR2-PDE3A. In one embodiment, at least one FGFR fusion is FGFR2-POC1B. In one embodiment, at least one FGFR fusion is FGFR2-SYNPO2. In one embodiment, at least one FGFR fusion is FGFR2-TACC2. In one embodiment, at least one FGFR fusion is FGFR2-TBC1D4. In one embodiment, at least one FGFR fusion is FGFR2-TRA2B. In one embodiment, at least one FGFR fusion is FGFR2-WAC. In one embodiment, at least one FGFR fusion is FGFR3-TACC3.

[0155] Also described herein is a method for treating cholangiocarcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cholangiocarcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-C382R and FGFR2-V395D. In one embodiment, the at least one FGFR mutation is FGFR2-C382R. In one embodiment, the at least one FGFR mutation is FGFR2-V395D.

[0156] Also described herein are methods for treating high-grade glioma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with high-grade glioma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-TACC1, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-TACC3, FGFR3-TMEM247, and FGFR2-IMPA1, or selected from FGFR1-TACC1, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-TACC3, and FGFR3-TMEM247. In one embodiment, the at least one FGFR fusion is FGFR1-TACC1. In one embodiment, the at least one FGFR fusion is FGFR3-ENOX1. In one embodiment, the at least one FGFR fusion is FGFR3-MYH14. In one embodiment, the at least one FGFR fusion is FGFR3-TACC3. In one embodiment, the at least one FGFR fusion is FGFR3-TMEM247. In one embodiment, the FGFR fusion is FGFR2-IMPA1.

[0157] Also described herein is a method for treating high-grade glioma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with high-grade glioma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0158] Also described herein are methods of treating pancreatic cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with pancreatic cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-MTUS1, FGFR2-ATAD2, FGFR2-CIT, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIF6, FGFR2-NRBF2, FGFR2-ALDH1L1, and FGFR2-KIAA1598. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-MTUS1, FGFR2-ATAD2, FGFR2-CIT, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIF6, FGFR2-NRBF2, FGFR2-ALDH1L1, FGFR2-KIAA1598, and FGFR2-PAWR. In one embodiment, the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-MTUS1, FGFR2-ATAD2, FGFR2-CIT, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIF6, FGFR2-NRBF2, and FGFR2-PTEN. In one embodiment, the at least one FGFR fusion is FGFR1-MTUS1. In one embodiment, the at least one FGFR fusion is FGFR2-ATAD2. In one embodiment, the at least one FGFR fusion is FGFR2-CIT. In one embodiment, the at least one FGFR fusion is FGFR2-GKAP1. In one embodiment, the at least one FGFR fusion is FGFR2-GPHN. In one embodiment, the at least one FGFR fusion is FGFR2-KCTD1.In one embodiment, at least one FGFR fusion is FGFR2-KIF6. In one embodiment, at least one FGFR fusion is FGFR2-NRBF2. In one embodiment, at least one FGFR fusion is FGFR2-PTEN. In one embodiment, at least one FGFR fusion is FGFR2-ALDH1L1. In one embodiment, at least one FGFR fusion is FGFR2-KIAA1598. In one embodiment, at least one FGFR fusion is FGFR2-PAWR.

[0159] Also described herein is a method of treating pancreatic cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with pancreatic cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0160] Also described herein are methods for treating squamous NSCLC, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous NSCLC and harboring at least one FGFR genetic mutation, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR3-TACC3, FGFR3-TACC2, and WDR11-FGFR2. In certain embodiments, the at least one FGFR fusion is FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR2-TACC2. In certain embodiments, the at least one FGFR fusion is WDR11-FGFR2.

[0161] Also described herein is a method for treating squamous NSCLC, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous NSCLC and carrying at least one FGFR gene mutation, wherein the at least one FGFR gene alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR3-R248C and FGFR3-S249C. In certain embodiments, the at least one FGFR mutation is FGFR3-R248C. In certain embodiments, the at least one FGFR mutation is FGFR3-S249C.

[0162] Also described herein are methods for treating non-squamous NSCLC, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with non-squamous NSCLC and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion or an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-BICC1, FGFR3-TACC3, and FGFR2-CCDC102A. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-BICC1, FGFR3-TACC3, FGFR2-CCDC102A, and FGFR2-TACC2. In one embodiment, the at least one FGFR fusion is FGFR2-BICC1. In one embodiment, at least one FGFR fusion is FGFR3-TACC3. In one embodiment, at least one FGFR fusion is FGFR2-CCDC102A. In one embodiment, at least one FGFR fusion is FGFR2-TACC2.

[0163] Also described herein is a method for treating non-squamous NSCLC, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with non-squamous NSCLC and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation or an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-Y375C, FGFR3-R399C, and FGFR3-S249C. In certain embodiments, the at least one FGFR mutation is FGFR2-Y375C. In certain embodiments, the at least one FGFR mutation is FGFR3-R399C. In certain embodiments, the at least one FGFR mutation is FGFR3-S249C.

[0164] Also described herein are methods of treating breast cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with breast cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-FKBP15, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TCERG1L, FGFR2-BICC1, and FGFR2-KIAA1598, or selected from FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-FKBP15, FGFR2-TACC2, FGFR2-TBC1D4, and FGFR2-TCERG1L. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-FKBP15, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TCERG1L, FGFR2-BICC1, FGFR2-KIAA1598, and CD44-FGFR2 FGFR2-FAM24B. In one embodiment, the at least one FGFR fusion is FGFR1-TACC1. In one embodiment, the at least one FGFR fusion is FGFR1-WHSC1L1. In one embodiment, the at least one FGFR fusion is WHSC1L1-FGFR1. In one embodiment, the at least one FGFR fusion is FGFR2-FKBP15. In one embodiment, the at least one FGFR fusion is FGFR2-TACC2. In one embodiment, at least one FGFR fusion is FGFR2-TBC1D4. In one embodiment, at least one FGFR fusion is FGFR2-TCERG1L. In one embodiment, at least one FGFR fusion is FGFR2-BICC1. In one embodiment, at least one FGFR fusion is FGFR2-KIAA1598. In one embodiment, at least one FGFR fusion is CD44-FGFR2.In one embodiment, at least one FGFR fusion is FGFR2-FAM24B.

[0165] Also described herein is a method for treating breast cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with breast cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation or an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-C382R, FGFR2-K659M, FGFR3-R248C, and FGFR3-Y375C, or selected from FGFR2-C382R and FGFR2-K659M. In one embodiment, the at least one FGFR mutation is FGFR2-C382R. In one embodiment, the at least one FGFR mutation is FGFR2-K659M. In one embodiment, the at least one FGFR mutation is FGFR3-R248C. In one embodiment, the at least one FGFR mutation is FGFR3-Y375C.

[0166] Also described herein are methods for treating colorectal cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with colorectal cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion or an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-BICC1 and FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR2-BICC1.

[0167] Also described herein are methods for treating colorectal cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally erdafitinib, to a patient diagnosed with colorectal cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation or an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-L770V, FGFR3-A500T, and FGFR3-F384L. In one embodiment, the at least one FGFR mutation is FGFR2-L770V. In one embodiment, the at least one FGFR mutation is FGFR3-A500T. In one embodiment, the at least one FGFR mutation is FGFR3-F384L.

[0168] Also described herein is a method of treating endometrial cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with endometrial cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0169] Also described herein are methods for treating endometrial cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with endometrial cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR1 mutation or an FGFR2 mutation. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-C382R, FGFR2-D101Y, FGFR2-L551F, and FGFR2-Y375C. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-S125L, FGFR2-C382R, FGFR2-D101Y, FGFR2-L551F, and FGFR2-Y375C. In one embodiment, at least one FGFR mutation is FGFR1-S125L. In one embodiment, at least one FGFR mutation is FGFR2-C382R. In one embodiment, at least one FGFR mutation is FGFR2-C382R. In one embodiment, at least one FGFR mutation is FGFR2-D101Y. In one embodiment, at least one FGFR mutation is FGFR2-L551F. In one embodiment, at least one FGFR mutation is FGFR2-Y375C.

[0170] Also described herein are methods for treating gastric cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gastric cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR3-TACC3 and FGFR2-HTRA1. In certain embodiments, the at least one FGFR fusion is FGFR3-TACC3. In certain embodiments, the FGFR fusion is FGFR2-HTRA1.

[0171] Also described herein is a method for treating gastric cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gastric cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation or an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-Y375C, FGFR3-S249C, and FGFR3-A500T. In one embodiment, the at least one FGFR mutation is FGFR2-Y375C. In one embodiment, the at least one FGFR mutation is FGFR3-S249C. In one embodiment, the at least one FGFR mutation is FGFR3-A500T.

[0172] Also described herein are methods for treating ovarian cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with ovarian cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion or an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-RHPN2, FGFR2-AGAP1, and FGFR2-CLOCK. In certain embodiments, the at least one FGFR fusion is selected from RHPN2-FGFR1, FGFR2-AGAP1, and FGFR2-CLOCK. In one embodiment, the at least one FGFR fusion is FGFR1-RHPN2. In one embodiment, the at least one FGFR fusion is RHPN2-FGFR1. In one embodiment, at least one FGFR fusion is FGFR2-AGAP1.In one embodiment, at least one FGFR fusion is FGFR2-CLOCK.

[0173] Also described herein is a method for treating ovarian cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with ovarian cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-S249C.

[0174] Also described herein are methods for treating cancer of unknown primary origin, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer of unknown primary origin and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-TBC1D5 and FGFR2-BICC1. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-TBC1D5, FGFR2-BICC1, FGFR2-CTNND2, and FGFR2-YPEL5. In one embodiment, the at least one FGFR fusion is FGFR2-TBC1D5. In one embodiment, the at least one FGFR fusion is FGFR2-BICC1. In one embodiment, at least one FGFR fusion is FGFR2-CTNND2. In one embodiment, at least one FGFR fusion is FGFR2-YPEL5.

[0175] Also described herein is a method for treating cancer of unknown primary origin, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cancer of unknown primary origin and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation or an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR3-S249C, FGFR2-S267P, and FGFR2-Y375C. In one embodiment, the at least one FGFR mutation is FGFR3-S249C. In one embodiment, the at least one FGFR mutation is FGFR2-S267P. In one embodiment, the at least one FGFR mutation is FGFR2-Y375C.

[0176] Also described herein are methods for treating cervical cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cervical cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion. In one embodiment, the FGFR fusion is an FGFR3 fusion. In one embodiment, the at least one FGFR mutation is FGFR3-TACC3.

[0177] Also described herein is a method for treating cervical cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with cervical cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-S249C.

[0178] Also described herein are methods of treating squamous cell head and neck cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous cell head and neck cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR3-TACC3 fusion.

[0179] Also described herein is a method for treating squamous cell head and neck cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous cell head and neck cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR3-S249C and FGFR3-S371G. In one embodiment, the at least one FGFR mutation is FGFR3-S249C. In one embodiment, the at least one FGFR mutation is FGFR3-S371G.

[0180] Also described herein are methods for treating esophageal cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with esophageal cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR3-JAKMIP1 and FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR3-JAKMIP1.

[0181] Also described herein is a method for treating esophageal cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with esophageal cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-R248C. In certain embodiments, the at least one FGFR mutation is FGFR3-A500T.

[0182] Also described herein are methods for treating low-grade glioma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with low-grade glioma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion, an FGFR2 fusion, or an FGFR1 fusion. In certain embodiments, the at least one FGFR fusion is selected from FGFR1-TACC1, FGFR2-VPS35, and FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR3-TACC3. In certain embodiments, the at least one FGFR fusion is FGFR2-VPS35. In certain embodiments, the at least one FGFR fusion is FGFR1-TACC1.

[0183] Also described herein are methods for treating low-grade glioma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with low-grade glioma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR1 mutation. In certain embodiments, the at least one FGFR mutation is FGFR1-K656E.

[0184] Also described herein is a method for treating prostate cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with prostate cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is FGFR3-WHSC1. In certain embodiments, the at least one FGFR fusion is WHSC1-FGFR3.

[0185] Also described herein is a method for treating prostate cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with prostate cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-R248C.

[0186] Also described herein are methods for treating salivary gland cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with salivary gland cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion. In certain embodiments, the at least one FGFR fusion is FGFR1-PLAG1. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation. In certain embodiments, the at least one FGFR mutation is FGFR2-C382R. In certain embodiments, the at least one FGFR genetic alteration is an FGFR fusion and an FGFR mutation. In certain embodiments, the FGFR fusion and the FGFR mutation are FGFR1-PLAG1 and FGFR2-C382R. Also described herein are methods for treating salivary gland cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with salivary gland cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation. In certain embodiments, the at least one FGFR mutation is selected from FGFR2-C382R, FGFR2-F276C, and FGFR2-Y375C. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, and FGFR2-Y375C. In one embodiment, at least one FGFR mutation is FGFR2-C382R. In one embodiment, at least one FGFR mutation is FGFR2-F276C. In one embodiment, at least one FGFR mutation is FGFR2-Y375C. In one embodiment, at least one FGFR mutation is FGFR2-E565A.In one embodiment, the at least one FGFR mutation is FGFR2-W72C. In one embodiment, the at least one FGFR mutation is FGFR2-E565A and FGFR2-W72C.

[0187] Also described herein is a method of treating basal cell carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with basal cell carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0188] Also described herein are methods for treating basal cell carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with basal cell carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation. In certain embodiments, the at least one FGFR mutation is FGFR2-S252L.

[0189] Also described herein are methods of treating thymic carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with thymic carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion. In certain embodiments, the at least one FGFR fusion is an IGSF3-FGFR1 fusion.

[0190] Also described herein is a method of treating thymic carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with thymic carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0191] Also described herein is a method of treating small intestinal adenocarcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with small intestinal adenocarcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0192] Also described herein is a method of treating small intestine adenocarcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with small intestine adenocarcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0193] Also described herein is a method of treating hepatocellular carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with hepatocellular carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0194] Also described herein is a method for treating hepatocellular carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with hepatocellular carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0195] Also described herein is a method of treating microcystic adnexal carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with microcystic adnexal carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0196] Also described herein is a method of treating microcystic adnexal carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with microcystic adnexal carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0197] Also described herein is a method of treating squamous cell carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous cell carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0198] Also described herein is a method for treating squamous cell carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with squamous cell carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0199] Also described herein is a method of treating gastrointestinal stromal tumor, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gastrointestinal stromal tumor and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0200] Also described herein is a method for treating gastrointestinal stromal tumors, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gastrointestinal stromal tumors and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-S249F.

[0201] Also described herein is a method for treating parathyroid carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with parathyroid carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR1 fusion. In certain embodiments, the at least one FGFR fusion is FGFR1-BAG4. In certain embodiments, the at least one FGFR fusion is BAG4-FGFR1.

[0202] Also described herein is a method of treating parathyroid carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with parathyroid carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0203] Also described herein are methods for treating soft tissue sarcoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with soft tissue sarcoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion, specifically an FGFR1 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR1-MTUS1 fusion.

[0204] Also described herein are methods for treating soft tissue sarcoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with soft tissue sarcoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR1 mutation. In certain embodiments, the at least one FGFR mutation is FGFR1-K656E.

[0205] Also described herein are methods for treating CUP syndrome, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with CUP syndrome and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR2-BICC1 fusion.

[0206] Also described herein is a method of treating CUP syndrome, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with CUP syndrome and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0207] Also described herein are methods of treating anal gland carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with anal gland carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0208] Also described herein are methods for treating anal gland carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with anal gland carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-R428C.

[0209] Also described herein is a method of treating anal adenoid cystic carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with anal adenoid cystic carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0210] Also described herein are methods for treating adenoid cystic carcinoma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with anal adenoid cystic carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation. In certain embodiments, the at least one FGFR mutation is FGFR2-P253L.

[0211] Also described herein is a method of treating conjunctival epidermoid carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with conjunctival epidermoid carcinoma and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0212] Also described herein is a method for treating conjunctival epidermoid carcinoma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with conjunctival epidermoid carcinoma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-S294C.

[0213] Also described herein are methods of treating duodenal cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with duodenal cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR2-TACC2 fusion.

[0214] Also described herein is a method of treating duodenal cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with duodenal cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0215] Also described herein is a method of treating gallbladder cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gallbladder cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0216] Also described herein are methods for treating gallbladder cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with gallbladder cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR2 mutation. In certain embodiments, the at least one FGFR mutation is FGFR2-Y375C.

[0217] Also described herein is a method of treating germ cell tumors, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with germ cell tumors and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0218] Also described herein is a method for treating germ cell tumors, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with germ cell tumors and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-P250R.

[0219] Also described herein are methods for treating mesothelioma, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with mesothelioma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR2-GOLGA2 fusion.

[0220] Also described herein is a method of treating mesothelioma, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with mesothelioma and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0221] Also described herein is a method of treating malignant small round cell tumors, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with malignant small round cell tumors and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion. In one embodiment, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion.

[0222] Also described herein is a method for treating malignant small round cell tumors, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with malignant small round cell tumors and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation, specifically an FGFR3 mutation. In certain embodiments, the at least one FGFR mutation is FGFR3-S249C.

[0223] Also described herein are methods for treating testicular cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with testicular cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR3 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR3-TACC3 fusion.

[0224] Also described herein is a method of treating testicular cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with testicular cancer and carrying at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0225] Also described herein are methods of treating thyroid cancer, comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with thyroid cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR fusion, specifically an FGFR2 fusion. In certain embodiments, the at least one FGFR fusion is an FGFR3-SENP6 fusion.

[0226] Also described herein is a method of treating thyroid cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient diagnosed with thyroid cancer and harboring at least one FGFR genetic alteration, wherein the at least one FGFR genetic alteration is an FGFR mutation. In one embodiment, the FGFR mutation is an FGFR1 mutation, an FGFR2 mutation, or an FGFR3 mutation.

[0227] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, generally erdafitinib, to a pediatric patient diagnosed with cancer and harboring at least one FGFR genetic alteration, wherein the cancer is glioblastoma multiforme, low-grade glioma, pilocytic astrocytoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, Ewing's sarcoma, or medulloblastoma. In certain embodiments, the patient is 6 to 18 years old. In certain embodiments, the patient is 6 to 12 years old. In certain embodiments, the patient is 12 to 15 years old. In certain embodiments, the patient is 15 to 18 years old. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0228] Also described herein are methods of treating glioblastoma multiforme, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of an FGFR inhibitor, specifically erdafitinib, to a pediatric patient diagnosed with glioblastoma multiforme and harboring at least one FGFR genetic alteration. In certain embodiments, the patient is 6 to 18 years of age. In certain embodiments, the patient is 6 to 12 years of age. In certain embodiments, the patient is 12 to 15 years of age. In certain embodiments, the patient is 15 to 18 years of age. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0229] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for treating a pediatric patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is glioblastoma multiforme, low-grade glioma, pilocytic astrocytoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, Ewing's sarcoma, or medulloblastoma. In certain embodiments, the patient is 6 to under 18 years of age. In certain embodiments, the patient is 6 to under 12 years of age. In certain embodiments, the patient is 12 to under 15 years of age. In certain embodiments, the patient is 15 to under 18 years of age. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0230] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for treating a pediatric patient diagnosed with glioblastoma multiforme and harboring at least one FGFR genetic alteration. In certain embodiments, the patient is 6 to under 18 years of age. In certain embodiments, the patient is 6 to under 12 years of age. In certain embodiments, the patient is 12 to under 15 years of age. In certain embodiments, the patient is 15 to under 18 years of age. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0231] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating cancer in a pediatric patient harboring at least one FGFR genetic alteration, wherein the cancer is glioblastoma multiforme, low-grade glioma, pilocytic astrocytoma, rhabdomyosarcoma, Wilms' tumor, neuroblastoma, Ewing's sarcoma, or medulloblastoma. In certain embodiments, the patient is 6 to 18 years old. In certain embodiments, the patient is 6 to 12 years old. In certain embodiments, the patient is 12 to 15 years old. In certain embodiments, the patient is 15 to 18 years old. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0232] Also described herein are FGFR inhibitors, specifically erdafitinib, for use in treating glioblastoma multiforme in pediatric patients harboring at least one FGFR genetic alteration. In certain embodiments, the patient is 6 to under 18 years old. In certain embodiments, the patient is 6 to under 12 years old. In certain embodiments, the patient is 12 to under 15 years old. In certain embodiments, the patient is 15 to under 18 years old. In certain embodiments, the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion, specifically an FGFR mutation or an FGFR fusion with an intact FGFR kinase domain.

[0233] Also described herein is a method of improving the objective response rate in a cancer patient or a population of cancer patients compared to a comparison population of cancer patients not treated with, generally, an FGFR inhibitor, specifically erdafitinib, the method comprising providing to the patient or population of patients a therapeutically effective amount of, generally, an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the objective response rate is assessed by an independent review committee. The objective response rate may be determined for individual patients or for a population of patients. In certain embodiments, the objective response rate for a population of cancer patients, specifically as assessed by an independent review committee, is about 29%. In certain embodiments, the objective response rate for a population of cancer patients, specifically as assessed by an independent review committee, is about 29.2%. In certain embodiments, the objective response rate for a population of cancer patients, specifically as assessed by an independent review committee, is at least about 29%. In certain embodiments, the objective response rate for a population of cancer patients, specifically as assessed by an independent review committee, is at least about 22%. In certain embodiments, the objective response rate for a population of cancer patients, particularly the objective response rate as assessed by an independent review committee, is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, or 36%. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, carcinoma of unknown primary site, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma. Also described herein are methods of treating cancer comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient population diagnosed with an advanced solid tumor, harboring a targeted FGFR mutation or fusion, who has progressed on or after at least one line of systemic therapy and who have no remaining treatment options with established clinical benefit, wherein the objective response rate in the patient population is as described above. In certain embodiments, the patient has been unable to tolerate standard treatment for the underlying tumor type.

[0234] Also described herein is a method of improving the objective response rate in a cancer patient or population of cancer patients harboring at least one FGFR gene fusion, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, comprising providing to the patient a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the objective response rate is assessed by an independent review committee. The objective response rate may be determined for individual or population patients. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is about 31.3 percent. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is about 30 percent. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is at least about 30 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 31 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 31 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 22 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, or 36%.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, cancer of unknown primary origin, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma.

[0235] Also described herein is a method of improving the objective response rate in a cancer patient or population of cancer patients harboring at least one FGFR gene mutation, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing to the patient a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the objective response rate is assessed by an independent review committee. The objective response rate may be determined for individual patients or for a population of patients. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is about 25.7 percent. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is about 26 percent. In certain embodiments, the objective response rate for a population of cancer patients, specifically the objective response rate as assessed by an independent review committee, is at least about 25.7 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 26.8 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 27 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 22 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 26 percent. In certain embodiments, the objective response rate for a population of cancer patients, particularly as assessed by an independent review committee, is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, or 36%.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, cancer of unknown primary origin, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma.

[0236] Also described herein are methods of improving the objective response rate in a cancer patient or population of cancer patients harboring at least one FGFR gene fusion, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing the patient with a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the objective response rate is assessed by an investigator. The objective response rate may be determined for individual patients or for a population of patients. In certain embodiments, the objective response rate for a population of cancer patients, specifically the investigator-assessed median duration of response, is at least about 26.4%. In certain embodiments, the objective response rate for a population of cancer patients, specifically the investigator-assessed objective response rate, is at least about 26 percent. In certain embodiments, the objective response rate for a population of cancer patients, specifically the investigator-assessed objective response rate, is at least about 22 percent. In certain embodiments, the objective response rate, particularly the investigator-assessed objective response rate, for a population of cancer patients is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, or 36%. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0237] Also described herein is a method of improving the median duration of response in a cancer patient or population of cancer patients compared to a comparison population of cancer patients not treated with, generally, an FGFR inhibitor, specifically erdafitinib, the method comprising providing to the patient a therapeutically effective amount of, generally, an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the median duration of response is assessed by an independent review committee. The median duration of response may be determined for an individual patient or for a population of patients. In certain embodiments, the median duration of response for a population of cancer patients, specifically as assessed by an independent review committee, is about 6.90 months. In certain embodiments, the median duration of response for a population of cancer patients, specifically as assessed by an independent review committee, is about 6.93 months. In certain embodiments, the median duration of response for a population of cancer patients, specifically as assessed by an independent review committee, is at least about 6.93 months. In certain embodiments, the median duration of response for a population of cancer patients, particularly as assessed by an independent review committee, is about 6.9 months. In certain embodiments, the median duration of response for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 6.9 months. In certain embodiments, the median duration of response for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 5.0 months. In certain embodiments, the median duration of response is about 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, at least about 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.1 months, 6.2 months, 6.3 months, 6.4 months, 6.5 months, 6.6 months, 6.7 months, 6.8 months, 6.9 months, 7.0 months, 7.1 months, 7.2 months, 7.3 months, 7.4 months, 7.5 months, 7.6 months, 7.8 months, 7.9 months, 8.0 months.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, cancer of unknown primary origin, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma.

[0238] Also described herein is a method of improving the median duration of response in a cancer patient or population of cancer patients compared to a comparison population of cancer patients not treated with, generally, an FGFR inhibitor, specifically erdafitinib, the method comprising providing to the patient a therapeutically effective amount of, generally, an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the median duration of response is assessed by an investigator. The median duration of response may be determined for an individual patient or for a population of patients. In certain embodiments, the median duration of response for a population of cancer patients, specifically, the investigator-assessed median duration of response, is about 7.1 months. In certain embodiments, the median duration of response for a population of cancer patients, specifically, the investigator-assessed median duration of response, is about 7 months. In certain embodiments, the median duration of response for a population of cancer patients, specifically, the investigator-assessed median duration of response, is at least about 7 months. In certain embodiments, the median duration of response for a population of cancer patients, particularly the investigator-assessed median duration of response, is at least about 5.0 months. In certain embodiments, the median duration of response is about 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, at least about 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.1 months, 6.2 months, 6.3 months, 6.4 months, 6.5 months, 6.6 months, 6.7 months, 6.8 months, 6.9 months, 7.0 months, 7.1 months, 7.2 months, 7.3 months, 7.4 months, 7.5 months, 7.6 months, 7.8 months, 7.9 months, or 8.0 months. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0239] Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient population diagnosed with an advanced solid tumor, harboring a targeted FGFR mutation or fusion, who has progressed on or after at least one line of systemic therapy, and who have no remaining treatment options with established clinical benefit, wherein the median duration of response in the patient population is as described above. In certain embodiments, the patient has failed to tolerate standard therapy for the underlying tumor type.

[0240] Also described herein is a method of improving disease control rates in a cancer patient or population of cancer patients compared to a comparison population of cancer patients not treated with, generally, an FGFR inhibitor, specifically erdafitinib, the method comprising providing to the patient a therapeutically effective amount of, generally, an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the disease control rate is assessed by an independent review committee. The disease control rate can be determined for individual patients or for a population of patients. In certain embodiments, the disease control rate for a population of cancer patients, specifically the disease control rate assessed by an independent review committee, is about 72.5%. In certain embodiments, the disease control rate for a population of cancer patients, specifically the disease control rate assessed by an independent review committee, is at least about 72% or at least about 72.5%. In certain embodiments, the disease control rate for a population of cancer patients, specifically the disease control rate assessed by an independent review committee, is about 77.4%. In certain embodiments, the disease control rate for a population of cancer patients, specifically the disease control rate assessed by an independent review committee, is at least about 77.4%. In certain embodiments, the disease control rate for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 75%. In certain embodiments, the disease control rate for a population of cancer patients, particularly as assessed by an independent review committee, is 72.0%, 72.5%, 73%, 73.5%, 74%, 74.5%, 75%, 75.5%, 76%, 76.6%, 77%, 77.7%, or 78%.In certain embodiments, the disease control rate for a population of cancer patients, specifically the disease control rate as assessed by an independent review committee, is 75.0%, 75.1%, 75.2%, 75.3%, 75.4%, 75.5%, 75.6%, 75.7%, 75.8%, 75.9%, 76.0%, 76.1%, 76.2%, 76.3%, 76.4%, 76.5%, 76.6%, 76.7%, 76.8%, 76.9%, 77.0%, 77.1%, 77.2%, 77.3%, 77.4%, 77.5%, 77.6%, 77.7%, 77.8%, 77.9%, 78.0%, 78.1%, 78.2%, 78.3%, 78.4%, 78.5%, 78.6%, 78.7%, 78.8%, 78.9%, or 79.0%. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, carcinoma of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, carcinoma of unknown primary origin, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma.Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient population diagnosed with an advanced solid tumor, harboring a targeted FGFR mutation or fusion, who has progressed on or after at least one line of systemic therapy, and who have no remaining treatment options with established clinical benefit, wherein the disease control rate in the patient population is as described above. In certain embodiments, the patient has been unable to tolerate standard therapy for the underlying tumor type.

[0241] Also described herein is a method for improving the median time to response in a cancer patient or population of cancer patients, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing the cancer patient with a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the disease control rate is assessed by an independent review committee. The median time to response can be determined for individual or population patients. In certain embodiments, the median time to response for a population of cancer patients, specifically the median time to response as assessed by an independent review committee, is at least about 1 month. In certain embodiments, the median time to response for a population of cancer patients, specifically the median time to response as assessed by an independent review committee, is about 1.4 months. In certain embodiments, the median time to response for a population of cancer patients, particularly the median time to response as assessed by an independent review committee, is about 1.0 month, 1.1 month, 1.2 months, 1.3 months, 1.4 months, 1.5 months, 1.6 months, 1.7 months, 1.8 months, 1.9 months, or 2.0 months. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, breast cancer, squamous non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, squamous head and neck cancer, cervical cancer, low-grade glioma, non-squamous NSCLC, esophageal cancer, cancer of unknown primary site, prostate cancer, salivary gland cancer, basal cell carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, or thymic carcinoma. Also described herein are methods of treating cancer, the methods comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more specifically erdafitinib, to a patient population diagnosed with an advanced solid tumor, harboring a targeted FGFR mutation or fusion, who has progressed on or after at least one line of systemic therapy and who have no remaining treatment options with established clinical benefit, wherein the median time to response in the patient population is as described above. In certain embodiments, the patient has been unable to tolerate standard treatment for the underlying tumor type.

[0242] Also described herein is a method of improving the clinical benefit rate in a cancer patient or population of cancer patients, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing the cancer patient with a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the clinical benefit rate is assessed by an independent review committee. The clinical benefit rate may be determined for an individual patient or a population of patients. In certain embodiments, the clinical benefit rate for a population of cancer patients, specifically as assessed by an independent review committee, is about 46.1%. In certain embodiments, the clinical benefit rate for a population of cancer patients, specifically as assessed by an independent review committee, is about 46%. In certain embodiments, the clinical benefit rate for a population of cancer patients, specifically as assessed by an independent review committee, is at least about 46%. In certain embodiments, the clinical benefit rate for a population of cancer patients, specifically as assessed by an independent review committee, is about 40% or at least about 40%. In certain embodiments, the clinical benefit rate for a population of cancer patients, particularly as assessed by an independent review committee, is 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0243] Also described herein is a method of improving median progression-free survival in a cancer patient or population of cancer patients, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing the patient with a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the median progression-free survival is assessed by an independent review committee. The median progression-free survival can be determined for an individual or population of patients. In certain embodiments, the median progression-free survival for a population of cancer patients, specifically the median progression-free survival assessed by an independent review committee, is about 4.2 months. In certain embodiments, the median progression-free survival for a population of cancer patients, specifically the median progression-free survival assessed by an independent review committee, is about 4 months. In certain embodiments, the median progression-free survival for a population of cancer patients, specifically the median progression-free survival assessed by an independent review committee, is at least about 4 months. In certain embodiments, the median progression-free survival for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 3 months. In certain embodiments, the median progression-free survival for a population of cancer patients, particularly as assessed by an independent review committee, is 3 months, 3.5 months, 4 months, or 4.5 months. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0244] Also described herein is a method of improving median overall survival in a cancer patient or population of cancer patients, generally compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib, the method comprising providing the patient with a therapeutically effective amount of generally an FGFR inhibitor, specifically erdafitinib. In certain embodiments, the median overall survival is assessed by an independent review committee. The median overall survival can be determined for an individual or population of patients. In certain embodiments, the median overall survival for a population of cancer patients, specifically median overall survival as assessed by an independent review committee, is about 10.94 months. In certain embodiments, the median overall survival for a population of cancer patients, specifically median overall survival as assessed by an independent review committee, is about 11 months. In certain embodiments, the median overall survival for a population of cancer patients, specifically median overall survival as assessed by an independent review committee, is at least about 11 months. In certain embodiments, the median overall survival for a population of cancer patients, particularly as assessed by an independent review committee, is at least about 9 months. In certain embodiments, the median overall survival for a population of cancer patients, particularly as assessed by an independent review committee, is 9 months, 9.5 months, 10 months, 10.5 months, 11 months, 11.5 months, or 12 months. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0245] In certain embodiments, administration of an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by objective response rate, median duration of response, disease control rate, median time to response, clinical benefit rate, progression-free survival, or overall survival, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administration of an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by objective response rate, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administration of an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by median duration of response, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administering an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by disease control rate, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administering an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by median time to response, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administering an FGFR inhibitor, particularly erdafitinib, generally provides improved anti-tumor activity, generally measured by clinical benefit rate, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, particularly erdafitinib. In certain embodiments, administration of an FGFR inhibitor generally, specifically erdafitinib, provides improved anti-tumor activity, generally as measured by progression-free survival, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, specifically erdafitinib.In certain embodiments, administration of an FGFR inhibitor generally, and in particular erdafitinib, provides improved anti-tumor activity, as measured by overall survival, compared to a comparison population of cancer patients not treated with an FGFR inhibitor, in particular erdafitinib.

[0246] In any of the aforementioned treatment methods, in certain embodiments, also described herein is a method of treating cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient who has been diagnosed with an advanced solid tumor, particularly any tumor or any of the tumors listed herein, who has a target FGFR mutation or fusion, particularly any FGFR mutation or fusion or any of the FGFR mutation or fusion listed herein, who has progressed on or after at least one line of systemic therapy, who has no remaining treatment options with established clinical benefit, and whose objective response rate in the patient population is as described above. In certain embodiments, the patient has been unable to tolerate standard treatment for the underlying tumor type.

[0247] In certain embodiments of any of the foregoing methods of treatment, also described herein is a method of treating cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient who has been diagnosed with an advanced solid tumor, particularly any tumor or any of the list of tumors provided herein, who has a targeted FGFR mutation or fusion, particularly any FGFR mutation or fusion or list of FGFR mutations or fusions provided herein, who has progressed on or after at least one line of systemic therapy, and who has no effective alternative therapy.

[0248] In certain embodiments of any of the foregoing methods of treatment, also described herein is a method of treating cancer, the method comprising, consisting of, or consisting essentially of administering a therapeutically effective amount of generally an FGFR inhibitor, more particularly erdafitinib, to a patient who has been diagnosed with a locally advanced solid tumor or a metastatic solid tumor, particularly any tumor or any list of tumors provided herein, who has a targeted FGFR mutation or fusion, particularly any FGFR mutation or fusion or list of FGFR mutations or fusions provided herein, who has progressed after prior therapy, and who has no accepted standard therapy.

[0249] In certain embodiments, the improved anti-tumor activity is compared to standard of care. In certain embodiments, the improved anti-tumor activity is compared to treatment generally with an FGFR inhibitor, specifically erdafitinib.

[0250] In some embodiments, the patient or population of patients to whom the FGFR inhibitor is administered and a comparison population of cancer patients generally not treated with an FGFR inhibitor, specifically erdafitinib, have both been previously treated with the same or similar prior treatment regimen.

[0251] In certain embodiments, the patient population is defined as the patient population that has completed the clinical trial detailed in the examples herein.In certain embodiments, the patient is an adult.In certain embodiments, the patient is an adolescent, optionally between 15 and 18 years old.In certain embodiments, the patient is an adolescent, optionally between 12 and 15 years old.In certain embodiments, the patient is a pediatric patient, optionally between 6 and 12 years old.

[0252] It is understood that for each of the therapeutic methods described herein, the therapeutic method can also be configured as a method for manufacturing a medicament for treating the described indication, or as a use for manufacturing a medicament for treating the described indication, or as an FGFR inhibitor generally, or specifically erdafitinib, for use in treating the described indication. In any of the described embodiments, the FGFR fusion can be any FGFR fusion in which the FGFR protein has an intact FGFR kinase domain. In certain embodiments, the FGFR fusion is an FGFR1 fusion, particularly an FGFR1 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR2 fusion, particularly an FGFR2 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR3 fusion, particularly an FGFR3 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion, particularly an FGFR1 fusion, an FGFR2 fusion, or an FGFR3 fusion described herein. In certain embodiments, the FGFR fusion is an FGFR2 fusion or an FGFR3 fusion, particularly an FGFR2 fusion or an FGFR3 fusion described herein. In certain embodiments, the FGFR mutation is an FGFR2 mutation, particularly an FGFR2 mutation described herein. In certain embodiments, the FGFR mutation is an FGFR3 mutation, particularly an FGFR3 mutation described herein. In certain embodiments, the FGFR mutation is an FGFR2 mutation or an FGFR3 mutation, particularly an FGFR2 mutation or an FGFR3 mutation described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR1 fusion, particularly an FGFR1 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR2 fusion, particularly an FGFR2 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR3 fusion, particularly an FGFR3 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR1, FGFR2, or FGFR3 fusion, particularly an FGFR1, FGFR2, or FGFR3 fusion described herein.In certain embodiments, the indication is an advanced solid tumor harboring an FGFR2 or FGFR3 fusion, particularly an FGFR2 or FGFR3 fusion described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR2 mutation, particularly an FGFR2 mutation described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR3 mutation, particularly an FGFR3 mutation described herein. In certain embodiments, the indication is an advanced solid tumor harboring an FGFR2 or FGFR3 mutation, particularly an FGFR2 or FGFR3 mutation described herein.

[0253] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT , FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y , FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA159 8, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR 2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, F GFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0254] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-AMOT, FGFR2-ATA D2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-E NOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR 2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-PO C1B, FGFR2-PTEN, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2- TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0255] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR 2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FG FR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, F GFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, F GFR2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1 D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0256] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-CTNND2, FGFR2-YPEL5, FGFR2-SENP6, FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGF R2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-C FAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2- K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGF R2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5 , FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

[0257] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD 2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M , FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGF R2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3 -S371G, FGFR3-TACC3, FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, FGFR3-P250R, or FGFR3-R399C.

[0258] In any of the described embodiments, the at least one FGFR gene alteration is selected from the group consisting of FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NO L4, FGFR2-PAWR, FGFR2-SENP6, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-TACC3, FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, or FGFR3-S249C.

[0259] In certain embodiments, the subject has received at least one line of systemic therapy prior to the administration of an FGFR inhibitor, specifically erdafitinib. The subject has received at least one line of systemic therapy prior to the administration of an FGFR inhibitor, specifically erdafitinib, in a metastatic setting. In one embodiment, the subject has progressed on or after at least one line of systemic therapy, and there is no additional available treatment with established clinical benefit prior to the administration of an FGFR inhibitor, specifically erdafitinib. In one embodiment, the subject has progressed after at least one line of systemic therapy prior to the administration of an FGFR inhibitor, specifically erdafitinib, and is unable to tolerate standard therapy.

[0260] In certain embodiments, the method or use further comprises, prior to said administration of erdafitinib, evaluating a biological sample from the patient for the presence of at least one FGFR fusion, particularly at least one FGFR fusion described herein, or at least one FGFR genetic alteration, particularly at least one FGFR genetic alteration described herein. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof. In certain embodiments, the method or use further comprises, prior to said administration of erdafitinib, evaluating a biological sample from the patient for the presence of at least one FGFR mutation, particularly at least one FGFR mutation described herein. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof.

[0261] In certain embodiments, the method or use further comprises, prior to said administration of erdafitinib, determining whether the patient has at least one FGFR fusion, particularly at least one FGFR fusion described herein, or at least one FGFR genetic alteration, particularly at least one FGFR genetic alteration described herein. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof. In certain embodiments, the method or use further comprises, prior to said administration of erdafitinib, determining whether the patient has at least one FGFR mutation, particularly at least one FGFR mutation described herein. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof.

[0262] In some embodiments, the patient is 15 years of age or older on the day of the first administration of the FGFR inhibitor. In certain embodiments, the patient is an adult 18 years of age or older. In certain embodiments, the patient is an adolescent between 15 and under 18 years of age. In further embodiments, the FGFR inhibitor, specifically erdafitinib, is administered daily, specifically once daily. In still further embodiments, the FGFR inhibitor, specifically erdafitinib, is administered orally. In certain embodiments, the FGFR inhibitor, specifically erdafitinib, is administered orally on a daily dosing schedule. In some embodiments, erdafitinib is administered orally at a dose of about 8 mg once daily. As used herein, "between" includes the smaller age range. For example, between 15 and under 18 years of age includes patients who are 15 years of age. Also, as used herein, the upper age range includes patients up to the day before they reach the indicated age, e.g., 18 years of age. In one embodiment, erdafitinib is administered at a dose of 8 mg, specifically 8 mg once daily, with the option to increase the dose to 9 mg depending on serum phosphorus levels (e.g., serum phosphorus levels below 7 mg / dL or in the range of 7 mg / dL to less than 9 mg / dL) and on observed treatment-related adverse events. In one embodiment, the serum phosphorus level used to determine whether to increase the dose is measured on a treatment day during the first cycle of erdafitinib treatment, specifically on day 14+2 of the first cycle of erdafitinib administration, more specifically on day 14 of the first cycle of erdafitinib administration. As used herein, the terms day 14 after initiation of treatment, day 14 of the first cycle of erdafitinib administration, day 14 of cycle 1, and C1D14 are used interchangeably. In some embodiments, erdafitinib is orally administered at a dose of about 8 mg once daily on a daily dosing schedule.In a further embodiment, if the patient exhibits a serum phosphate (PO4) level of less than about 7.0 mg / dL, the dose of erdafitinib is increased from 8 mg / day to 9 mg / day after initiation of treatment, specifically, if the patient exhibits a serum PO4 level of less than about 7.0 mg / dL on day 14, optionally day 14+2, specifically on day 14, after initiation of treatment, the dose of erdafitinib is increased from 8 mg / day to 9 mg / day after initiation of treatment. In a further embodiment, if the patient exhibits a serum PO4 level in the range of 7.0 mg / dL or more but less than 9.0 mg / dL, the dose of erdafitinib is increased from 8 mg / day to 9 mg / day after the start of treatment; specifically, if the patient exhibits a serum PO4 level in the range of about 7.0 mg / dL or more but less than 9.0 mg / dL on day 14, optionally on day 14+2, specifically on day 14, after the start of treatment, the dose of erdafitinib is increased from 8 mg / day to 9 mg / day after the start of treatment. In certain embodiments, the increase in the dose of erdafitinib from 8 mg to 9 mg is performed with the administration of a phosphate binder, specifically, if the patient exhibits a serum PO4 level in the range of 7.0 mg / dL or more but less than 9.0 mg / dL. In certain embodiments, the phosphate binder is sevelamer. In certain embodiments, 8 mg per day is 8 mg once daily. In certain embodiments, 9 mg per day is 9 mg once daily.

[0263] In some embodiments, the patient is between 12 and under 15 years of age on the date of first administration of the FGFR inhibitor. As used herein, "between" includes the lower age range. For example, between 12 and under 15 years of age includes patients who are 12 years old. Also, as used herein, the upper age range includes patients up to the day before the patient turns the indicated age, e.g., 15 years of age. In one embodiment, erdafitinib is administered at a dose of 5 mg, specifically 5 mg once daily, with the option of increasing the dose to 6 mg, specifically 6 mg once daily, and the further option of increasing the dose to 8 mg, specifically 8 mg once daily, depending on serum phosphorus levels (e.g., serum phosphorus levels less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL) and depending on any treatment-related adverse events observed. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose, specifically from 5 mg once daily to 6 mg once daily, is measured on a treatment day during the first cycle of erdafitinib treatment, specifically within 14+2 days of erdafitinib administration, more specifically on day 14 of the first cycle of erdafitinib administration. As used herein, day 14 after initiation of treatment, day 14 of the first cycle of erdafitinib administration, day 14 of cycle 1, and C1D14 are used interchangeably. If the patient exhibits a serum phosphorus concentration less than 7 mg / dL or in the range of 7.0 mg / dL to 9.0 mg / dL, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment. In certain embodiments, the dose increase of erdafitinib from 5 mg once daily to 6 mg once daily is performed with the administration of a phosphate binder, specifically when the patient exhibits a serum PO level in the range of 7.0 mg / dL or greater and less than 9.0 mg / dL. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose, specifically whether to increase the dose from 5 mg once daily to 6 mg once daily, is measured on a treatment day during the second cycle of erdafitinib treatment, specifically on day 7 of the second cycle of erdafitinib administration (day 7 of cycle 2 or C2D7).If a patient exhibits a serum phosphorus concentration of less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment. In certain embodiments, the increase in the dose of erdafitinib from 5 mg once daily to 6 mg once daily is performed, specifically if a patient exhibits a serum PO4 level in the range of 7.0 mg / dL to less than 9.0 mg / dL, accompanied by administration of a phosphate binder. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose from 6 mg once daily to 8 mg once daily after already increasing the dose to 6 mg on C1D14+2, more specifically on C1D14, is measured on a treatment day during the second cycle of erdafitinib treatment, specifically on day 7 of the second cycle of erdafitinib administration (day 7 of cycle 2 or C2D7). If the patient exhibits a serum phosphorus concentration of less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL, the dose of erdafitinib is increased from 6 mg / day to 8 mg / day after initiation of treatment. In certain embodiments, the increase in the dose of erdafitinib from 6 mg once daily to 8 mg once daily is performed with the administration of a phosphate binder, particularly if the patient exhibits a serum PO4 level in the range of 7.0 mg / dL to less than 9.0 mg / dL. In certain embodiments, the phosphate binder is sevelamer. In certain embodiments, 5 mg per day is 5 mg once daily. In certain embodiments, 6 mg per day is 6 mg once daily. In certain embodiments, 8 mg per day is 8 mg once daily.

[0264] In certain embodiments, erdafitinib is administered at a dose of about 5 mg once daily. In a further embodiment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO4) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 or 14, optionally on day 14+2, specifically on day 14, from the start of treatment. In a further embodiment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO4) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 or 14, optionally on day 14+2, specifically on day 14, from the start of treatment. In a further embodiment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 of the second cycle of erdafitinib treatment. In a further embodiment, the dose of erdafitinib is further increased from 6 mg / day to 8 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 14, optionally on day 14+2, specifically on day 14, from the start of treatment. In certain embodiments, the dose of erdafitinib is further increased from 6 mg / day to 8 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 of the second cycle of erdafitinib treatment. In certain embodiments, the dose increase of erdafitinib from 5 mg to 6 mg or from 6 mg to 8 mg is performed with the administration of a phosphate binder, specifically if the patient exhibits a serum PO4 level in the range of 7.0 mg / dL or more and less than 9.0 mg / dL on day 14 after the start of treatment or on day 7 of the second cycle of treatment. In certain embodiments, the phosphate binder is sevelamer. In yet a further embodiment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after the start of treatment if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 7 or 14, optionally on day 14+2, specifically on day 14 after the start of treatment.In yet a further embodiment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 14, optionally on day 14+2, specifically on day 14, after initiation of treatment. In yet a further embodiment, if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 7 of the second cycle of erdafitinib treatment, the dose of erdafitinib is increased from 5 mg / day to 6 mg / day after initiation of treatment, and in a further embodiment, if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 14, optionally on day 14+2, specifically on day 14, after initiation of treatment, the dose of erdafitinib is further increased from 6 mg / day to 8 mg / day after initiation of treatment. In a further embodiment, the dose of erdafitinib is further increased from 6 mg / day to 8 mg / day after initiation of treatment if the patient exhibits a serum PO level of less than 7.0 mg / dL on day 7 of the second cycle of erdafitinib treatment. In a further embodiment, the two dose escalations (5 mg to 6 mg and 6 mg to 8 mg) are stepwise, i.e., the subject is not allowed to escalate directly from 5 mg to 8 mg.

[0265] In some embodiments, if the patient is between 6 and under 12 years old on the first administration date of the FGFR inhibitor, specifically erdafitinib, the FGFR inhibitor, specifically erdafitinib, is administered at a dose of about 3 mg, specifically 3 mg once daily. As used herein, "between" includes the smaller age range. For example, between 6 and under 12 years old includes patients aged 6 years. Also, as used herein, the upper age range includes patients up to the day before they reach the indicated age, e.g., 12 years old. In one embodiment, erdafitinib is administered at a dose of 3 mg, specifically at a dose of 3 mg once daily, with the option of increasing the dose to 4 mg, specifically 4 mg once daily, depending on the serum phosphorus concentration (e.g., if the serum phosphorus concentration is less than 7 mg / dL, or is greater than 7 mg / dL and less than 9 mg / dL, specifically greater than 7.0 mg / dL and less than 9.0 mg / dL), and depending on the treatment-related adverse events observed, with the further option of increasing the dose from 4 mg to 5 mg, specifically 5 mg once daily. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose is measured on the treatment day during the first cycle of erdafitinib treatment, specifically on day 14+2 of the first cycle of erdafitinib administration, more specifically on day 14. As used herein, day 14 after initiation of treatment, day 14 of the first cycle of erdafitinib administration, day 14 of cycle 1, and C1D14 are used interchangeably. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose is measured on a treatment day during the second cycle of erdafitinib treatment, specifically on day 7 of the second cycle of erdafitinib administration (day 7 of cycle 2 or C2D7). In certain embodiments, erdafitinib is administered at a dose of about 3 mg once daily. In a further embodiment, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after initiation of treatment if, on day 14 after initiation of treatment, optionally on day 14+2, the patient exhibits a serum phosphate (PO4) level in the range of 7.0 mg / dL or greater but less than 9 mg / dL.In a further embodiment, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 of the second cycle of erdafitinib treatment. In certain embodiments, the dose of erdafitinib is further increased from 4 mg / day to 5 mg / day after initiation of treatment if the patient exhibits a serum phosphate (PO) level in the range of 7.0 mg / dL or greater to less than 9 mg / dL on day 7 of the second cycle of erdafitinib treatment. In certain embodiments, the increase in the dose of erdafitinib from 3 mg to 4 mg or from 4 mg to 5 mg is performed in combination with the administration of a phosphate binder, such as sevelamer, particularly if the patient exhibits a serum PO level in the range of 7.0 mg / dL or greater to less than 9.0 mg / dL on day 14 after initiation of treatment or on day 7 of the second cycle of treatment. In certain embodiments, the dose increase of erdafitinib from 3 mg to 4 mg or from 4 mg to 5 mg is performed in combination with the administration of a phosphate binder, e.g., sevelamer, if the serum PO4 level is in the range of 7.0 mg / dL or greater but less than 9.0 mg / dL on day 14, optionally day 14+2, specifically day 14, or on day 7 of the second cycle of erdafitinib treatment after initiation of treatment. In yet a further embodiment, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after initiation of treatment if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 14, optionally day 14+2, specifically day 14, after initiation of treatment. In yet a further embodiment, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after initiation of treatment if the patient exhibits a serum PO4 level of less than 7.0 mg / dL on day 7 of the second cycle of erdafitinib treatment. In a further embodiment, the dose of erdafitinib is further increased from 4 mg / day to 5 mg / day after initiation of treatment if the patient exhibits a serum PO level of less than 7.0 mg / dL on day 7 of the second cycle of erdafitinib treatment. In a further embodiment, the two dose escalations (3 mg to 4 mg and 4 mg to 5 mg) are stepwise, i.e., the subject is not allowed to escalate directly from 3 mg to 5 mg.In certain embodiments, 3 mg per day is 3 mg once a day. In certain embodiments, 4 mg per day is 4 mg once a day. In certain embodiments, 5 mg per day is 5 mg once a day.

[0266] In some embodiments, the patient is between 6 and under 12 years old on the day of the first administration of the FGFR inhibitor. As used herein, "between" includes the lower age range. For example, between 6 and under 12 years old includes patients who are 6 years old. Also, as used herein, the upper age range includes patients up to the day before they reach the indicated age, e.g., 12 years old. In one embodiment, erdafitinib is administered at a dose of 3 mg, specifically 3 mg once daily, with the option to increase the dose to 4 mg, specifically 4 mg once daily, and the further option to increase the dose to 5 mg, specifically 5 mg once daily, depending on serum phosphorus levels (e.g., serum phosphorus levels less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL) and on any treatment-related adverse events observed. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose, specifically from 3 mg once daily to 4 mg once daily, is measured on a treatment day during the first cycle of erdafitinib treatment, specifically on day 14+2 of erdafitinib administration, more specifically on day 14 of the first cycle of erdafitinib administration. As used herein, day 14 after initiation of treatment, day 14 of the first cycle of erdafitinib administration, day 14 of cycle 1, and C1D14 are used interchangeably. If a patient exhibits a serum phosphorus concentration less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after initiation of treatment. In certain embodiments, specifically when a patient exhibits a serum PO4 level in the range of 7.0 mg / dL or greater and less than 9.0 mg / dL, an erdafitinib dose increase from 3 mg once daily to 4 mg once daily is performed in conjunction with administration of a phosphate binder. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose, specifically from 3 mg once daily to 4 mg once daily, is measured on a treatment day during the second cycle of erdafitinib treatment, specifically on day 7 of the second cycle of erdafitinib administration (day 7 of cycle 2 or C2D7).If a patient exhibits a serum phosphorus concentration of less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL, the dose of erdafitinib is increased from 3 mg / day to 4 mg / day after the start of treatment. In certain embodiments, specifically if a patient exhibits a serum PO4 level in the range of 7.0 mg / dL to less than 9.0 mg / dL, an erdafitinib dose increase from 3 mg once daily to 4 mg once daily is performed with the administration of a phosphate binder. In one embodiment, the serum phosphorus concentration for determining whether to increase the dose from 4 mg once daily to 5 mg once daily, which has already been increased to 4 mg, on C1D14+2, more specifically on C1D14, is measured on the treatment day during the second cycle of erdafitinib treatment, specifically on day 7 of the second cycle of erdafitinib administration (day 7 of cycle 2 or C2D7). If the patient exhibits a serum phosphorus concentration of less than 7 mg / dL or in the range of 7.0 mg / dL to less than 9.0 mg / dL, the dose of erdafitinib is increased from 4 mg / day to 5 mg / day after initiation of treatment. In certain embodiments, the increase in the dose of erdafitinib from 4 mg once daily to 5 mg once daily is performed with the administration of a phosphate binder, particularly if the patient exhibits a serum PO4 level in the range of 7.0 mg / dL to less than 9.0 mg / dL. In certain embodiments, the phosphate binder is sevelamer. In certain embodiments, 3 mg per day is 3 mg once daily. In certain embodiments, 4 mg per day is 4 mg once daily. In certain embodiments, 5 mg per day is 5 mg once daily.

[0267] In certain embodiments, erdafitinib is administered in a solid dosage form. In further embodiments, the solid dosage form is a tablet.

[0268] Treatment with erdafitinib should be interrupted or modified based on erdafitinib-associated toxicities, as described in Table A.

[0269] [Table 2]

[0270] Subjects with any grade of toxicity (grades 1-4) should be offered symptomatic treatment, if applicable.

[0271] If erdafitinib is discontinued for one or more consecutive weeks due to drug-related toxicity, the study drug may be reintroduced after recovery from toxicity, either at the same dose level or at the original reduced dose level (see dose reduction levels in Tables B, C, and D). A second dose reduction may be performed following a second occurrence of drug-related toxicity.

[0272] If erdafitinib must be withheld for more than 28 days due to a drug-related adverse event that cannot be resolved to an acceptable level (e.g., Grade 1 or less non-hematologic toxicity or return to baseline), erdafitinib treatment should be discontinued unless the subject is deriving benefit from treatment and the investigator can demonstrate that continued treatment with erdafitinib is in the subject's best interest. Erdafitinib may be resumed at the same or lower dose (Tables B, C, and D) if the sponsor's medical monitor agrees with the evaluation.

[0273] If erdafitinib is dose reduced and the adverse event that was the reason for this dose reduction has completely resolved, the dose may be re-escalated to the next higher dose if the subject is deriving benefit from treatment and the investigator can demonstrate that a re-escalation of the erdafitinib dose is in the subject's best interest and the medical monitor agrees with the evaluation.

[0274] In all cases of clinically significant impaired wound healing or impending surgery or potential bleeding complications, it is recommended that dose administration be interrupted, appropriate clinical laboratory data (e.g., coagulation parameters) be carefully monitored, and supportive care be administered if necessary. Dose administration may be resumed if it is deemed safe and appropriate according to the investigator's assessment.

[0275] [Table 3]

[0276] [Table 4]

[0277] [Table 5]

[0278] Described herein are FGFR inhibitors, specifically erdafitinib, for use in treating cancer in patients harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The FGFR inhibitor should be administered at a therapeutically effective dose.

[0279] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating cancer in patients harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose.

[0280] Also described herein are FGFR inhibitors, specifically erdafitinib, for use in treating cancer in patients harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. The FGFR inhibitor should be administered at a therapeutically effective dose.

[0281] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating cancer in patients harboring at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose.

[0282] Further described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2. In certain embodiments, the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1. The FGFR inhibitor should be administered at a therapeutically effective dose.

[0283] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for treating a patient diagnosed with cancer and harboring an alteration in at least one FGFR gene, wherein the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, and parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose.

[0284] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. The FGFR inhibitor should be administered at a therapeutically effective dose.

[0285] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for treating a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma. The FGFR inhibitor must be administered at a therapeutically effective dose.

[0286] Also described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. The FGFR inhibitor should be administered at a therapeutically effective dose.

[0287] Evaluation of the sample for the presence of one or more FGFR gene alterations

[0010] Described herein are methods of treating cancer, comprising, consisting of, or consisting essentially of: evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR fusion is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0288] Described herein are methods of treating cancer, comprising, consisting of, or consisting essentially of: evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR fusion is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0289] Also described herein are methods of treating cancer, comprising, consisting of, or consisting essentially of: determining whether a patient diagnosed with cancer harbors at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if the patient harbors at least one FGFR fusion. In one embodiment, the FGFR inhibitor is erdafitinib. Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR fusion, erdafitinib is administered or should be administered if one or more FGFR fusions are present in the sample.

[0290] Also described herein are methods of treating cancer, comprising, consisting of, or consisting essentially of: determining whether a patient diagnosed with cancer possesses at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if the patient possesses at least one FGFR fusion. In one embodiment, the FGFR inhibitor is erdafitinib. Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and harboring at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR fusion, erdafitinib is administered or should be administered if one or more FGFR fusions are present in the sample.

[0291] Also described herein are FGFR inhibitors, specifically erdafitinib, for use in treating patients who have been diagnosed with cancer and who harbor at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR fusion, erdafitinib is administered or should be administered if one or more FGFR fusions are present in the sample.

[0292] Also described herein are FGFR inhibitors, specifically erdafitinib, for use in treating patients who have been diagnosed with cancer and who harbor at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR fusion, erdafitinib is administered or should be administered if one or more FGFR fusions are present in the sample.

[0293] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of: evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma; and administering to the patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR genetic alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0294] Also described herein is a method of treating cancer, comprising evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR gene alteration, including, but not limited to, cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous head and neck cancer, esophageal cancer, and low-grade glioma. and administering to the patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR alteration is present in the sample. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0295] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0296] Also described herein is a method of treating cancer, comprising evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one FGFR gene alteration, wherein the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, and prostate cancer. , salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR alteration is present in the sample. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0297] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of determining whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR genetic alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0298] Also described herein is a method of treating cancer, comprising determining whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, The method comprises, consists of, or consists essentially of: determining that the cancer is salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR gene alteration is present in the sample. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0299] Also described herein is a method of treating cancer, comprising, consisting of, or consisting essentially of determining whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma, and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR genetic alteration is present in the sample. In one embodiment, the FGFR inhibitor is erdafitinib.

[0300] Also described herein is a method of treating cancer, comprising determining whether a patient diagnosed with cancer harbors at least one FGFR genetic alteration, the cancer being selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, The method comprises, consists of, or consists essentially of: determining that the cancer is salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; and administering a therapeutically effective dose of an FGFR inhibitor to the patient if at least one FGFR gene alteration is present in the sample. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary site, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer. In one embodiment, the FGFR inhibitor is erdafitinib.

[0301] Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR fusion, wherein erdafitinib is administered or should be administered if one or more FGFR alterations are present in a biological sample from the patient after evaluating the sample for the presence of at least one FGFR alteration, and the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0302]

[0003] Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR fusion, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample, and the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer, and the like. The use of an FGFR inhibitor is for the following cancers: non-squamous NSCLC (NSCLC), breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal gland carcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0303] Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR fusion, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample, and the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0304]

[0010] Described herein is the use of an FGFR inhibitor, specifically erdafitinib, for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and carrying at least one FGFR fusion, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample, and the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, non-small cell squamous cell carcinoma, and cholangiocarcinoma. Use of an FGFR inhibitor if the cancer is lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal gland carcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0305] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating a patient diagnosed with cancer and harboring at least one FGFR fusion, wherein erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, and the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0306] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating a patient diagnosed with cancer and harboring at least one FGFR fusion, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, if one or more FGFR alterations are present in the sample, erdafitinib is administered or should be administered, and the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, non-small cell lung cancer, and squamous cell carcinoma. The cancer is lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; or an FGFR inhibitor. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0307] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating a patient diagnosed with cancer and carrying at least one FGFR fusion, wherein erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, and the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous NSCLC, non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

[0308] Also described herein is an FGFR inhibitor, specifically erdafitinib, for use in treating a patient diagnosed with cancer and harboring at least one FGFR fusion, wherein after evaluating a biological sample from the patient for the presence of at least one FGFR alteration, erdafitinib is administered or should be administered if one or more FGFR alterations are present in the sample, and the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, non-small cell squamous cell carcinoma, and cholangiocarcinoma. The cancer is lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary origin, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid carcinoma, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; or an FGFR inhibitor. In certain embodiments, the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary origin, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

[0309] The following methods for evaluating a biological sample for the presence of one or more FGFR genetic alterations or for determining whether a patient carries one or more FGFR genetic alterations apply equally to any of the methods of treatment and methods of use disclosed above.

[0310] The disclosed methods are suitable for treating cancer in a patient when one or more FGFR genetic alterations are present in a biological sample from the patient. In some embodiments, the FGFR genetic alterations can be one or more FGFR fusion genes, specifically one or more FGFR1, FGFR2, or FGFR3 fusion genes. In some embodiments, the FGFR genetic alterations can be one or more FGFR mutations, specifically one or more FGFR1 mutations, FGFR2 mutations, or FGFR3 mutations. In some embodiments, a combination of one or more FGFR genetic alterations can be present in a biological sample from a patient. For example, in some embodiments, the FGFR genetic alterations can be one or more FGFR fusion genes and one or more FGFR mutations.

[0311] Exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR1-ALDH1L1, FGFR2 ... GFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2 -ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KI F6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2- S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V 395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1, or a combination thereof.

[0312] In certain embodiments, exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-AMOT, FGFR1-ALPHA, FGFR1-ALPHA- ... FR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2 -ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KI F6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2 -PTEN, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-T FGFR3-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1, or a combination thereof.

[0313] In certain embodiments, exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1 L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2 -KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3 A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1 L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-ENOX1, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1, or a combination thereof.

[0314] Exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-CTNND2, FGFR2-YPEL5, FGFR2-SENP6, FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2 -AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR 2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2- PDE3A, FGFR2-POC1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGF These include, but are not limited to, R2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1, or a combination thereof.

[0315] Exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD 2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FG FR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-PO C1B, FGFR2-S252L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VP S35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGF R3-TACC3, FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, FGFR3-P250R, or FGFR3-R399C, or a combination thereof,Not limited to these.

[0316] Exemplary FGFR alterations are provided in Table 9, Table 14, or Table 19, and exemplary FGFR alterations include FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NOL4, FGFR2-P FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-TACC3, FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, or FGFR3-S249C, or a combination thereof.

[0317] Suitable methods for evaluating a biological sample for the presence of one or more FGFR genetic alterations are described in the methods section herein and in International Publication No. 2016 / 048833 and U.S. Patent Application No. 16 / 723,975, which are incorporated herein by reference in their entireties. For example, and without intending to be limiting, evaluating a biological sample for the presence of one or more FGFR genetic alterations can include any combination of the following steps: isolating RNA from the biological sample, synthesizing cDNA from the RNA, and amplifying the cDNA (pre-amplified or not). In some embodiments, evaluating a biological sample for the presence of one or more FGFR genetic alterations can include amplifying cDNA from the patient using a primer pair that binds to and amplifies one or more genetic alterations and determining whether one or more FGFR genetic alterations are present in the sample. In some aspects of the present disclosure, the cDNA can be pre-amplified. In some aspects of the present disclosure, the evaluating step can include isolating RNA from the sample, synthesizing cDNA from the isolated RNA, and pre-amplifying the cDNA.

[0318] The presence of one or more FGFR gene alterations can be assessed at any suitable time point, including at the time of diagnosis, following tumor removal, following the first line of treatment, during clinical treatment, or any combination thereof.

[0319] For example, a biological sample taken from a patient can be analyzed to determine whether a condition or disease, such as cancer, that the patient is suffering from or may be suffering from is characterized by genetic abnormalities or aberrant protein expression that result in upregulation of FGFR levels or activity, or sensitization of pathways to normal FGFR activity, or upregulation of these growth factor signaling pathways, such as growth factor ligand levels or growth factor ligand activity, or upregulation of biochemical pathways downstream of FGFR activation.

[0320] Examples of such abnormalities that lead to activation or sensitization of FGFR signaling include loss or inhibition of apoptosis pathways, upregulation of receptors or ligands, or genetic alterations of receptors or ligands, such as the presence of PTK mutants. Tumors with genetic alterations of FGFR1, FGFR2, FGFR3, or FGFR4, or upregulation, particularly overexpression, of FGFR1, or gain-of-function genetic alterations of FGFR2 or FGFR3 may be particularly sensitive to FGFR inhibitors.

[0321] The methods, approved formulations, and uses may further comprise assessing the presence of one or more FGFR genetic alterations in the biological sample prior to the administering step.

[0322] Diagnostic tests and screenings are typically performed on biological samples selected from tumor biopsy samples, blood samples (isolation and enrichment of sloughed tumor cells), fecal biopsies, sputum, chromosome analysis, pleural effusion, ascites, buccal spears, biopsies, circulating DNA, or urine. In certain embodiments, the biological sample is blood, lymph, bone marrow, a solid tumor sample, or any combination thereof. In certain embodiments, the biological sample is a solid tumor sample. In certain embodiments, the biological sample is a blood sample. In certain embodiments, the biological sample is a urine sample.

[0323] Methods for identifying and analyzing genetic alterations and protein upregulation are well known in the art, and screening methods can include standard methods such as reverse-transcriptase polymerase chain reaction (RT-PCR) or in situ hybridization such as fluorescence in situ hybridization (FISH).

[0324] Identification of individuals with genetic alterations in FGFR, particularly those described herein, may indicate that the patient is particularly suitable for treatment with an FGFR inhibitor, specifically erdafitinib. Tumors can be selectively screened for the presence of FGFR mutations prior to treatment. Screening processes typically involve direct sequencing, oligonucleotide microarray analysis, or mutant-specific antibodies. Furthermore, diagnosis of tumors with such genetic alterations can be performed using methods such as RT-PCR, FISH, or next-generation sequencing, as well known to those skilled in the art and described herein.

[0325] Furthermore, genetic alterations of, for example, FGFRs can be identified by, for example, direct sequencing of tumor biopsies using PCR and methods for direct sequencing of PCR products as described above. Those skilled in the art will recognize that any such well-known techniques for detecting overexpression, activation, or mutation of the above proteins can be applied in the context of the present invention.

[0326] In RT-PCR screening, the level of mRNA in tumors is assessed by generating a cDNA copy of the mRNA and then amplifying the cDNA by PCR. PCR amplification methods, primer selection, and amplification conditions are well known to those skilled in the art. Nucleic acid manipulation and PCR are performed by standard methods described, for example, in Ausubel, FM et al., eds. (2004) Current Protocols in Molecular Biology, John Wiley & Sons Inc., or Innis, MA et al., eds. (1990) PCR Protocols: a guide to methods and applications, Academic Press, San Diego. Reactions and manipulations involving nucleic acid technology are also described in Sambrook et al., (2001), 3rd Ed., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press. Alternatively, commercially available kits for RT-PCR (e.g., Roche Molecular Biochemicals) may be used, or the methodology set forth in U.S. Patent Nos. 4,666,828, 4,683,202, 4,801,531, 5,192,659, 5,272,057, 5,882,864, and 6,218,529 may be used, which are incorporated herein by reference. An example of an in situ hybridization technique for assessing mRNA expression is fluorescence in situ hybridization (FISH) (see Angerer (1987) Meth. Enzymol., 152:649).

[0327] Generally, in situ hybridization involves the following major steps: (1) fixation of the tissue to be analyzed; (2) prehybridization treatment of the sample to increase the accessibility of the target nucleic acid and reduce nonspecific binding; (3) hybridization of a mixture of nucleic acids with nucleic acids in a biological structure or tissue; (4) posthybridization washes to remove nucleic acid fragments not bound by hybridization; and (5) detection of the hybridized nucleic acid fragments. Probes used in such applications are typically labeled, for example, with radioisotopes or fluorescent reporters. Preferred probes are sufficiently long to allow specific hybridization with the target nucleic acid under stringent conditions, for example, from about 50, 100, or 200 nucleotides to about 1000 nucleotides or more. Standard methods for performing FISH are described in Ausubel, F M et al., eds. (2004) Current Protocols in Molecular Biology, John Wiley & Sons Inc. and Fluorescence In Situ Hybridization: Technical Overview by John M S Bartlett in Molecular Diagnosis of Cancer, Methods and Protocols, 2nd ed. ISBN: 1-59259-760-2; March 2004, pp. 077-088; Series: Methods in Molecular Medicine.

[0328] The method for gene expression profiling is described in (DePrimo et al., (2003), BMC Cancer, 3:3). Briefly, the protocol is as follows: Double-stranded cDNA is synthesized from total RNA using a (dT)24 oligomer to prime first-strand cDNA synthesis, followed by second-strand cDNA synthesis using a random hexamer primer. This double-stranded cDNA is used as a template for in vitro transcription of cRNA using biotinylated ribonucleotides. The cRNA is chemically fragmented according to the protocol described by Affymetrix (Santa Clara, CA, USA), and then hybridized overnight on a Human Genome Array.

[0329] Alternatively, the protein products expressed from mRNA may be assayed by immunohistochemistry of tumor samples, solid-phase immunoassays using microtiter plates, Western blotting, two-dimensional SDS-polyacrylamide gel electrophoresis, ELISA, flow cytometry, and other methods well known in the art for detecting specific proteins. Detection methods include the use of site-specific antibodies. Those skilled in the art will recognize that any such well-known techniques for detecting FGFR upregulation or FGFR mutants or variants may be applicable in the context of the present invention.

[0330] Abnormal levels of proteins such as FGFR can be measured using standard enzyme assays, such as those described herein. Activation or overexpression can also be detected in tissue samples (e.g., tumor tissues). Tyrosine kinase activity can be measured using assays such as those from Chemicon International. The tyrosine kinase of interest is immunoprecipitated from the sample lysate and its activity measured.

[0331] Another method for measuring the overexpression or activation of FGFR, including its isoforms, is to measure microvessel density, which can be measured, for example, using the method described by Orre and Rogers (Int J Cancer (1999), 84(2)101-8). Assay methods also include the use of markers.

[0332] Thus, any of these techniques can also be used to identify tumors particularly suitable for treatment with the compounds of the invention.

[0333] Pharmaceutical Compositions and Routes of Administration Given their useful pharmacological properties, FGFR inhibitors in general, and erdafitinib more specifically, can be formulated into various pharmaceutical forms for administration purposes.

[0334] In one embodiment, a pharmaceutical composition (e.g., formulation) comprises at least one FGFR inhibitor together with one or more pharmaceutically acceptable carriers, adjuvants, excipients, diluents, fillers, buffers, stabilizers, preservatives, lubricants, or other materials known to those skilled in the art, and optionally other therapeutic or prophylactic agents.

[0335] To prepare a pharmaceutical composition, an effective amount of an FGFR inhibitor, more specifically erdafitinib, as an active ingredient is generally combined with a pharmaceutically acceptable carrier, which can take various forms depending on the desired dosage form. The pharmaceutical composition can be in any form suitable for oral, parenteral, topical, intranasal, ocular, otic, rectal, vaginal, or transdermal administration. These pharmaceutical compositions are preferably in a unit dosage form suitable for oral, rectal, transdermal, or parenteral injection administration. For example, when preparing an inhibitor as an oral dosage form, any of the usual pharmaceutical media can be used, such as water, glycols, oils, and alcohols for oral liquid preparations such as suspensions, syrups, elixirs, and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, and disintegrants for powders, pills, capsules, and tablets.

[0336] The pharmaceutical compositions of the present invention, particularly capsules and / or tablets, can include one or more pharmaceutically acceptable excipients (pharmaceutically acceptable carriers), such as disintegrants, diluents, fillers, binders, buffers, glidants, glidants, thickeners, sweeteners, flavoring agents, coloring agents, preservatives, etc. Some excipients can serve multiple purposes.

[0337] Suitable disintegrants have a large swelling coefficient. Examples include hydrophilic cross-linked polymers that are insoluble or poorly soluble in water, such as crospovidone (cross-linked polyvinylpyrrolidone) and croscarmellose sodium (cross-linked sodium carboxymethylcellulose). The amount of disintegrant in the tablet of the present invention may conveniently be in the range of about 2.5 to about 15% (w / w), preferably in the range of about 2.5 to 7% (w / w), and particularly in the range of about 2.5 to 5% (w / w). Since disintegrants inherently result in sustained-release formulations when used in large amounts, it is advantageous to dilute the disintegrant with an inert substance called a diluent or filler.

[0338] A variety of materials can be used as diluents or fillers. Examples include lactose monohydrate, anhydrous lactose, sucrose, dextrose, mannitol, sorbitol, starch, cellulose (e.g., microcrystalline cellulose (Avicel™), silicified microcrystalline cellulose), dihydrate or anhydrous dibasic calcium phosphate, and others known in the art, as well as mixtures thereof (e.g., the spray-dried mixture of lactose monohydrate (75%) and microcrystalline cellulose (25%) commercially available as Microcelac™). Microcrystalline cellulose and mannitol are preferred. The total amount of diluent or filler in the pharmaceutical compositions of the present invention may conveniently range from about 20% to about 95% (w / w), preferably from about 55% to about 95% (w / w), or from about 70% to about 95% (w / w), or from about 80% to about 95% (w / w), or from about 85% to about 95%.

[0339] Lubricants and glidants can be used in the manufacture of certain dosage forms, and are usually used when manufacturing tablets. Examples of lubricants and glidants include hydrogenated vegetable oils, such as hydrogenated cottonseed oil, magnesium stearate, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silica, colloidal anhydrous silica, talc, mixtures thereof, and others known in the art. Interesting lubricants are magnesium stearate and mixtures of magnesium stearate and colloidal silica, with magnesium stearate being preferred. A preferred lubricant is colloidal anhydrous silica.

[0340] When present, lubricants generally comprise 0.2 to 7.0% (w / w) of the total composition weight, specifically 0.5 to 1.5% (w / w), and more specifically 1 to 1.5% (w / w).

[0341] When present, lubricants generally constitute 0.2 to 7.0% (w / w) of the total composition weight, specifically 0.2 to 2% (w / w), or 0.5 to 2% (w / w), or 0.5 to 1.75% (w / w), or 0.5 to 1.5% (w / w).

[0342] A binder may optionally be used in the pharmaceutical compositions of the present invention. Suitable binders are water-soluble polymers, such as alkylcelluloses, for example, methylcellulose; hydroxyalkylcelluloses, for example, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxybutylcellulose; hydroxyalkylalkylcelluloses, for example, hydroxyethylmethylcellulose and hydroxypropylmethylcellulose; carboxyalkylcelluloses, for example, carboxymethylcellulose; alkali metal salts of carboxyalkylcelluloses, for example, sodium carboxymethylethylcellulose; carboxyalkylalkylcelluloses, for example, carboxymethylethylcellulose; carboxyalkylcellulose esters; starch; pectins, for example, sodium carboxymethylamylopectin; chitin derivatives, for example, chitosan; disaccharides, oligosaccharides, and polysaccharides, for example, trehalose, cyclodextrin and derivatives thereof, alginic acid, alkali metal and ammonium salts thereof, carrageenan, galactomannan, tragacanth, agar, gum arabic, guar gum, and xanthan gum; polyacrylic acid and salts thereof; polymethacrylic acid, salts and esters thereof, methacrylate copolymers; polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and copolymers thereof, for example, PVP-VA. Preferably, the water-soluble polymer is a hydroxyalkyl alkyl cellulose, such as hydroxypropyl methyl cellulose, (eg, hydroxypropyl methyl cellulose 15 cps).

[0343] Other excipients, such as colorants and pigments, can also be added to the compositions of the present invention. Colorants and pigments include titanium dioxide and food-grade dyes. Colorants or pigments are optional ingredients in the formulations of the present invention, but if used, the colorant can be present in an amount of up to 3.5% (w / w) based on the total composition weight.

[0344] Flavoring agents are optional in the composition and can be selected from synthetic flavor oils and flavoring aromatics or natural oils, extracts from plant leaves, flowers, fruits, and the like, and combinations thereof. These can include cinnamon oil, oil of wintergreen, peppermint oil, bay oil, anise oil, eucalyptus oil, and thyme oil. Also useful as flavoring agents are vanilla, citrus oils such as lemon, orange, grape, lime, and grapefruit, and fruit essences such as apple, banana, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot, and the like. The amount of flavoring agent can depend on several factors, including the desired organoleptic effect. Generally, flavoring agents are present in an amount of about 0% to about 3% (w / w).

[0345] Formaldehyde scavengers are compounds capable of absorbing formaldehyde. Formaldehyde scavengers include compounds containing nitrogen centers reactive with formaldehyde, forming one or more reversible or irreversible bonds between the formaldehyde scavenger and formaldehyde. For example, formaldehyde scavengers contain one or more nitrogen atoms / centers that react with formaldehyde to form a Schiff base imine that can subsequently bind to formaldehyde. For example, formaldehyde scavengers contain one or more nitrogen centers that react with formaldehyde to form one or more 5- to 8-membered rings. Formaldehyde scavengers preferably contain one or more amine or amide groups. For example, formaldehyde scavengers can be amino acids, amino sugars, α-amine compounds, or conjugates or derivatives thereof, or mixtures thereof. Formaldehyde scavengers may contain two or more amines and / or amides.

[0346] Formaldehyde scavengers include, for example, glycine, alanine, serine, threonine, cysteine, valine, leucine, isoleucine, methionine, phenylalanine, tyrosine, aspartic acid, glutamic acid, arginine, lysine, ornithine, citrulline, taurine, pyrrolysine, meglumine, histidine, aspartame, proline, tryptophan, citrulline, pyrrolysine, asparagine, glutamine, or conjugates or mixtures thereof; or, where possible, pharmaceutically acceptable salts thereof.

[0347] In one aspect of the invention, the formaldehyde scavenger is meglumine or a pharmaceutically acceptable salt thereof, specifically meglumine base.

[0348] In one embodiment, in the methods and uses described herein, erdafitinib is or should be administered as a pharmaceutical composition, particularly a tablet or capsule, comprising erdafitinib or a pharmaceutically acceptable salt thereof, particularly erdafitinib base, a formaldehyde scavenger, particularly meglumine or a pharmaceutically acceptable salt thereof, particularly meglumine base, and a pharmaceutically acceptable carrier.

[0349] Another object of the present invention is to provide a process for preparing the pharmaceutical composition described herein, particularly in the form of a tablet or capsule, characterized by blending a formaldehyde scavenger, particularly meglumine, and erdafitinib, a pharmaceutically acceptable salt thereof or a solvate thereof, particularly erdafitinib base, with a pharmaceutically acceptable carrier, and compressing the blend into a tablet or filling the blend into a capsule.

[0350] Because of their ease of administration, tablets and capsules are the most advantageous oral dosage unit forms, in which case solid pharmaceutical carriers are obviously used. For parenteral compositions, the carrier usually comprises, at least in large part, sterile water, although other ingredients, for example, to aid solubility, may be included. For example, injectable solutions can be prepared in which the carrier comprises saline, glucose solution, or a mixture of saline and glucose solution. Injectable suspensions may also be prepared, in which case appropriate liquid carriers, suspending agents, etc. may be used. In compositions suitable for transdermal administration, the carrier optionally comprises a penetration enhancer and / or a suitable humectant, optionally in combination with a small amount of any suitable additive that does not cause significant adverse effects on the skin. Such additives may facilitate application to the skin and / or aid in formulating the desired composition. These compositions can be administered in a variety of ways, for example, as a transdermal patch, a spot-on, or an ointment. It is particularly advantageous to formulate the above pharmaceutical compositions into dosage unit forms for ease of administration and uniformity of dosage. As used in this specification and claims, unit dosage form refers to physically discrete units suitable as single dosages, each containing a predetermined quantity of active ingredient calculated to produce a desired therapeutic effect, in association with the required pharmaceutical carrier. Examples of such unit dosage forms are tablets (including scored or coated tablets), capsules, pills, powder packets, wafers, injectable solutions or suspensions, teaspoons, tablespoons, and the like, and multiples thereof.

[0351] It is particularly advantageous to formulate the above-mentioned pharmaceutical composition into unit dosage form for ease of administration and uniform dosage.As used herein, unit dosage refers to a physically discrete unit suitable as a single dose, each unit containing a predetermined amount of active ingredient calculated to produce a desired therapeutic effect together with necessary pharmacological carriers.Examples of such unit dosage forms are tablets (including scored tablets or coated tablets), capsules, pills, powder packets, wafers, injectable solutions or suspensions, teaspoons, tablespoons, etc., and multiple portions thereof.Preferred forms are tablets and capsules.

[0352] In certain embodiments, the FGFR inhibitor is present in a solid unit dosage form and is suitable for oral administration. The unit dosage form may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg of the FGFR inhibitor per unit dosage form, or an amount within a range defined by two of these values, particularly an amount of 3, 4, or 5 mg per unit dose.

[0353] Depending on the mode of administration, the pharmaceutical composition preferably comprises 0.05 to 99% by weight, more preferably 0.1 to 70% by weight, even more preferably 0.1 to 50% by weight of the FGFR inhibitor and 1 to 99.95% by weight, more preferably 30 to 99.9% by weight, even more preferably 50 to 99.9% by weight of the pharmaceutically acceptable carrier, all percentages being based on the total weight of the composition.

[0354] The tablets or capsules of the present invention may be further film-coated, for example, to improve taste, ease of swallowing, and provide an elegant appearance. Polymer-based film coating materials are well known in the art. A water-based film coating is preferred over a solvent-based film coating, since the latter may contain more trace aldehydes. A preferred film coating material is the Opadry® II aqueous film coating system, e.g., Opadry® II 85F, such as Opadry® II 85F92209. Further preferred film coatings are water-based film coatings that protect against environmental moisture, such as aqueous moisture-proof film coating systems, such as Readilycoat® (e.g., Readilycoat® D), AquaPolish® MS, Opadry® amb, and Opadry® amb II. A preferred film coating is Opadry® amb II, a high-performance moisture-proof film coating that is a polyethylene glycol-free PVA-based immediate-release system.

[0355] In tablets according to the invention, the film coat preferably comprises by weight no more than about 4% (w / w) of the total tablet weight.

[0356] Of the capsules according to the present invention, hypromellose (HPMC) capsules are preferred over gelatin capsules.

[0357] In one aspect of the present invention, the pharmaceutical compositions described herein, specifically in capsule or tablet form, contain 0.5 mg to 20 mg base equivalent, or 2 mg to 20 mg base equivalent, or 0.5 mg to 12 mg base equivalent, or 2 mg to 12 mg base equivalent, or 2 mg to 10 mg base equivalent, or 2 mg to 6 mg base equivalent, or 2 mg base equivalent, 3 mg base equivalent, 4 mg base equivalent, 5 mg base equivalent, 6 mg base equivalent, 7 mg base equivalent, 8 mg base equivalent, 9 mg base equivalent, 10 mg base equivalent, 11 mg base equivalent, or 12 mg base equivalent of erdafitinib, a pharmaceutically acceptable salt thereof, or a solvate thereof. Specifically, the pharmaceutical compositions described herein contain 3 mg base equivalent, 4 mg base equivalent, or 5 mg base equivalent of erdafitinib, a pharmaceutically acceptable salt thereof, or a solvate thereof, specifically 3 mg, 4 mg, or 5 mg of erdafitinib base.

[0358] In one aspect of the invention, particularly in capsule or tablet form, the pharmaceutical compositions described herein contain 0.5 mg to 20 mg, or 2 mg to 20 mg, or 0.5 mg to 12 mg, or 2 mg to 12 mg, or 2 mg to 10 mg, or 2 mg to 6 mg, or 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, or 12 mg of erdafitinib base. Specifically, the pharmaceutical compositions described herein contain 3 mg, 4 mg, or 5 mg of erdafitinib base. Specifically, the pharmaceutical compositions described herein contain 3 mg, 4 mg, or 5 mg of erdafitinib base and about 0.5 to about 5% (w / w), about 0.5 to about 3% (w / w), about 0.5 to about 2% (w / w), about 0.5 to about 1.5% (w / w), or about 0.5 to about 1% (w / w) of a formaldehyde scavenger, specifically meglumine. Specifically, the pharmaceutical compositions described herein contain 3 mg, 4 mg, or 5 mg of erdafitinib base and about 0.5 to about 1.5% (w / w) or about 0.5 to about 1% (w / w) of a formaldehyde scavenger, specifically meglumine.

[0359] In one embodiment of the present invention, multiple (e.g., two) pharmaceutical compositions described herein can be administered to obtain a desired dose, e.g., a daily dose. For example, for a daily dose of erdafitinib at 8 mg base equivalent, two tablets or capsules each containing 4 mg of erdafitinib base equivalent can be administered. Alternatively, a tablet or capsule containing 3 mg of erdafitinib base equivalent and a tablet or capsule containing 5 mg of base equivalent can be administered. For example, for a daily dose of erdafitinib at 9 mg base equivalent, three tablets or capsules each containing 3 mg of erdafitinib base equivalent can be administered. Alternatively, a tablet or capsule containing 4 mg of erdafitinib base equivalent and a tablet or capsule containing 5 mg of base equivalent can be administered.

[0360] The amount of formaldehyde scavenger, specifically meglumine, in the pharmaceutical composition according to the present invention can be in the range of about 0.1 to about 10% (w / w), about 0.1 to about 5% (w / w), about 0.1 to about 3% (w / w), about 0.1 to about 2% (w / w), about 0.1 to about 1.5% (w / w), about 0.1 to about 1% (w / w), about 0.5 to about 5% (w / w), about 0.5 to about 3% (w / w), about 0.5 to about 2% (w / w), about 0.5 to about 1.5% (w / w), or about 0.5 to about 1% (w / w).

[0361] According to certain embodiments, erdafitinib is supplied as 3 mg, 4 mg, or 5 mg film-coated tablets for oral administration containing the following inactive ingredients or their equivalents: tablet core: croscarmellose sodium, magnesium stearate, mannitol, meglumine, and microcrystalline cellulose; and film coating: Opadry amb II: glycerol monocaprylocaprate type I, partially hydrolyzed polyvinyl alcohol, sodium lauryl sulfate, talc, titanium dioxide, yellow iron oxide, red iron oxide (for orange and brown tablets), triiron tetroxide / black iron oxide (for brown tablets).

[0362] Safety studies seek to identify any potential adverse effects that may result from exposure to a drug. Efficacy is often measured by determining whether an active pharma...

Claims

1. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises erdafitinib or a pharma- ceutical acceptable salt thereof, The method comprises administering a therapeutically effective amount of erdafitinib, or a pharma- ceutical acceptable salt thereof, to a patient diagnosed with cancer and having at least one fibroblast growth factor receptor (FGFR) fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2, comprising a pharmaceutical composition.

2. 2. The pharmaceutical composition of claim 1, wherein the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1.

3. The pharmaceutical composition of claim 1 or 2, wherein the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

4. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-CCDC102A.

5. The pharmaceutical composition of claim 4, wherein the cancer is non-squamous non-small cell lung cancer (NSCLC).

6. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-CCDC147.

7. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-ENOX1.

8. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-LCN10.

9. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-PDE3A.

10. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-RANBP2.

11. The pharmaceutical composition of claim 1, wherein the FGFR fusion is RRM2B-FGFR2.

12. The pharmaceutical composition according to any one of claims 6 to 11, wherein the cancer is bile duct cancer.

13. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR2-GPHN.

14. The pharmaceutical composition of claim 13 , wherein the cancer is pancreatic cancer.

15. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR3-ENOX1.

16. The pharmaceutical composition of claim 1, wherein the FGFR fusion is FGFR3-TMEM247.

17. The pharmaceutical composition of claim 15 or 16, wherein the cancer is high-grade glioma.

18. The pharmaceutical composition of claim 1, wherein the FGFR fusion is IGSF3-FGFR1.

19. The pharmaceutical composition of claim 18, wherein the cancer is thymic carcinoma.

20. The pharmaceutical composition of claim 1, wherein the FGFR fusion is RHPN2-FGFR1.

21. The pharmaceutical composition of claim 20, wherein the cancer is ovarian cancer.

22. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises erdafitinib or a pharma- ceutical acceptable salt thereof, The method comprises administering a therapeutically effective amount of erdafitinib or a pharma- ceutical acceptable salt thereof to a patient diagnosed with cancer and having at least one fibroblast growth factor receptor (FGFR) genetic alteration, wherein the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, carcinoma of unknown primary, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, and parathyroid carcinoma.

23. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises erdafitinib or a pharma- ceutical acceptable salt thereof, The method comprises administering a therapeutically effective amount of erdafitinib or a pharma- ceutical acceptable salt thereof to a patient diagnosed with cancer and having at least one fibroblast growth factor receptor (FGFR) genetic alteration, wherein the cancer is selected from the group consisting of cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid cancer, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, and thyroid cancer.

24. 24. The pharmaceutical composition of claim 23, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

25. 24. The pharmaceutical composition of claim 22 or 23, wherein the at least one FGFR genetic alteration is an FGFR mutation or an FGFR fusion.

26. The at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, FGFR1-BAG4, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, FGFR1-RHPN2, FGFR1-TACC1, FGFR1-WHSC1L1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR 2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR 2-F276C, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-KIF6, FGFR2 -L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2-NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-S252 L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TBC1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V 395D, FGFR2-VPS35, FGFR2-WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3, FGFR3-TMEM247, or FGFR3-WHSC1.

27. The at least one FGFR gene alteration is selected from the group consisting of FGFR1-PLAG1, FGFR2-C382R, BAG4-FGFR1, IGSF3-FGFR1, FGFR1-K656E, FGFR1-MTUS1, RHPN2-FGFR1, FGFR1-TACC1, WHSC1L1-FGFR1, FGFR2-AGAP1, FGFR2-AHCYL1, FGFR2-ALDH1L1, FGFR2-AMOT, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-CD2AP, FGFR2-CFAP57, FGFR2-CFAP1, FGFR2-CFAP2, FGFR2-CFAP1 ... GFR2-CIT, FGFR2-CLOCK, FGFR2-D101Y, FGFR2-ENOX1, FGFR2-F276C, FGFR 2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-K659M, FGFR2-KCTD1, FGFR2 -KIAA1598, FGFR2-KIF6, FGFR2-L551F, FGFR2-L770V, FGFR2-LGSN, FGFR2 -NOL4, FGFR2-NRBF2, FGFR2-PAWR, FGFR2-PDE3A, FGFR2-POC1B, FGFR2-S25 2L, FGFR2-S267P, FGFR2-SYNPO2, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TB C1D5, FGFR2-TCERG1L, FGFR2-TRA2B, FGFR2-V395D, FGFR2-VPS35, FGFR2- WAC, FGFR2-Y375C, FGFR3-A500T, FGFR3-ENOX1, FGFR3-F384L, FGFR3-MYH 14, FGFR3-R248C, FGFR3-S249C, FGFR3-S249F, FGFR3-S371G, FGFR3-TACC3 , FGFR3-TMEM247, WHSC1-FGFR3, CD44-FGFR2, FGFR2-CTNND2, FGFR2-FAM24B, FGFR2-GOLGA2, FGFR2-HTRA1, FGFR2-IMPA1, FGFR2-SENP6, FGFR2-YPEL5, FGFR3-JAKMIP1, WDR11-FGFR2, FGFR1-S125L, FGFR2-E565A, FGFR2-P253L, FGFR2-W72C, FGFR3-P250R, or FGFR3-R399C.

28. The at least one FGFR gene alteration is selected from the group consisting of FGFR1-MTUS1, FGFR1-PLAG1, FGFR1-TACC1, FGFR2-ATAD2, FGFR2-BICC1, FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-FKBP15, FGFR2-GKAP1, FGFR2-GPHN, FGFR2-KCTD1, FGFR2-KIAA1598, FGFR2-NOL4, FGFR2-PAWR, FG 28. The pharmaceutical composition of claim 27, which is FR2-SENP6, FGFR2-TACC2, FGFR2-TBC1D4, FGFR2-TRA2B, FGFR2-VPS35, FGFR2-WAC, FGFR3-TACC3, FGFR1-K656E, FGFR2-C382R, FGFR2-E565A, FGFR2-F276C, FGFR2-W72C, FGFR2-Y375C, FGFR3-R248C, or FGFR3-S249C.

29. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein the subject has received at least one line of systemic therapy prior to administration of the erdafitinib or a pharma- ceutically acceptable salt thereof.

30. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein the method further comprises evaluating a biological sample from the patient for the presence of the at least one FGFR fusion or the at least one FGFR genetic alteration prior to administration of the erdafitinib or a pharma- ceutically acceptable salt thereof.

31. 31. The pharmaceutical composition of claim 30, wherein the biological sample is a blood, lymph, bone marrow, a solid tumor sample, or any combination thereof.

32. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is administered daily.

33. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is administered orally.

34. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is administered orally on a daily dosing schedule.

35. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein the patient is 15 years of age or older on the day of the first administration of erdafitinib or a pharma- ceutical acceptable salt thereof.

36. The pharmaceutical composition described in claim 35, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is erdafitinib.

37. 37. The pharmaceutical composition of claim 36, wherein erdafitinib is administered once daily at a dose of about 8 mg, or erdafitinib is administered once daily at a dose of about 9 mg, particularly erdafitinib is administered once daily at a dose of about 8 mg.

38. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein the patient is between 12 and 15 years of age on the day of the first administration of erdafitinib or a pharma- ceutical acceptable salt thereof.

39. The pharmaceutical composition described in claim 38, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is erdafitinib.

40. 40. The pharmaceutical composition of claim 39, wherein erdafitinib is administered once daily at a dose of about 5 mg, or erdafitinib is administered once daily at a dose of about 6 mg, or erdafitinib is administered once daily at a dose of about 8 mg, in particular, erdafitinib is administered once daily at a dose of about 5 mg.

41. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein the patient is between 6 and 12 years of age on the day of the first administration of erdafitinib or a pharma- ceutical acceptable salt thereof.

42. The pharmaceutical composition described in claim 41, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is erdafitinib.

43. 43. The pharmaceutical composition of claim 42, wherein erdafitinib is administered once daily at a dose of about 3 mg, or erdafitinib is administered once daily at a dose of about 4 mg, or erdafitinib is administered once daily at a dose of about 5 mg, in particular, erdafitinib is administered once daily at a dose of about 3 mg.

44. 24. The pharmaceutical composition of any one of claims 1, 22 and 23, wherein erdafitinib or a pharma- ceutically acceptable salt thereof is administered in a solid dosage form.

45. 45. The pharmaceutical composition of claim 44, wherein the solid dosage form is a tablet.

46. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises an FGFR inhibitor, The method comprises: evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one fibroblast growth factor receptor (FGFR) fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2; - administering to said patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR fusion is present in said sample.

47. 47. The pharmaceutical composition of claim 46, wherein the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1.

48. 48. The pharmaceutical composition of claim 46 or 47, wherein the FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

49. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises an FGFR inhibitor, The method comprises: - evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one fibroblast growth factor receptor (FGFR) gene alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma; - administering to said patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR genetic alteration is present in said sample.

50. 1. A pharmaceutical composition for use in a method of treating cancer, comprising: The pharmaceutical composition comprises an FGFR inhibitor, The method comprises: - evaluating a biological sample from a patient diagnosed with cancer for the presence of at least one fibroblast growth factor receptor (FGFR) gene alteration, the cancer being cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid cancer, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer; - administering to said patient a therapeutically effective dose of an FGFR inhibitor if at least one FGFR genetic alteration is present in said sample.

51. 51. The pharmaceutical composition of claim 50, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

52. 51. The pharmaceutical composition of any one of claims 46, 49 and 50, wherein the FGFR inhibitor is erdafitinib.

53. 16. Use of erdafitinib for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and having at least one FGFR fusion selected from FGFR2-CCDC102A, FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, RHPN2-FGFR1, and RRM2B-FGFR2.

54. 54. The use of claim 53, wherein the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1.

55. 55. The use of claim 54, wherein the at least one FGFR fusion is selected from FGFR2-CCDC102A, FGFR2-ENOX1, and FGFR2-GPHN.

56. Use of erdafitinib for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and having at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous cell head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic carcinoma, small intestine adenocarcinoma, hepatocellular carcinoma, microcystic adnexal carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or parathyroid carcinoma.

57. 2. Use of erdafitinib for the manufacture of a medicament for the treatment of a patient diagnosed with cancer and having at least one FGFR genetic alteration, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, cancer of unknown primary site, cervical cancer, squamous head and neck cancer, esophageal cancer, low-grade glioma, prostate cancer, salivary gland cancer, basal cell carcinoma, thymic cancer, gastrointestinal stromal tumor, parathyroid cancer, soft tissue sarcoma, adenoid cystic carcinoma, anal adenocarcinoma, conjunctival epidermoid carcinoma, duodenal cancer, gallbladder cancer, germ cell tumor, malignant small round cell tumor, mesothelioma, testicular cancer, or thyroid cancer.

58. 58. The use of claim 57, wherein the cancer is cholangiocarcinoma, high-grade glioma, pancreatic cancer, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, breast cancer, endometrial cancer, ovarian cancer, cancer of unknown primary, squamous head and neck cancer, esophageal cancer, low-grade glioma, salivary gland cancer, duodenal cancer, or thyroid cancer.

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