Cancer treatment

Abstract

To provide a method for the treatment of cancer with erdafitinib.SOLUTION: The present invention provides a method for the treatment of cancer, which method comprises administering, to a subject in need thereof, in particular a cancer patient, an amount of erdafitinib so that the level of serum phosphate is within the range of 5.5 mg / dL to less than 7 mg / dL, including 5.5 mg / dL, or within the range of 5.5 mg / dL to 9 mg / dL or less, including 5.5 mg / dL.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention has the potential to reduce the likelihood of high reactions while limiting potential toxicities, such as nail toxicity. The present invention provides a method for treating cancer with erdafitinib.

[0002] The present invention provides an erdafitinib-based drug that maximizes erdafitinib exposure while limiting potential toxicity. Treatment of cancer with fibronectin is provided.

[0003] The present invention provides a high objective response rate, specifically an objective response rate of at least 40%, specifically has an objective response rate of at least 40% in chemotherapy-naïve cancer patients, with one prior line of chemotherapy At least a 40% objective response rate in cancer patients with disease progression after chemotherapy, At least 40% of cancer patients who had disease progression after two or more prior lines of chemotherapy The present invention provides treatment of cancer with erdafitinib having an objective response rate of .

[0004] The present invention has a short time to response, specifically a median time to response of less than 2 months. The present invention provides a method for treating cancer with erdafitinib. [Brief description of the drawings]

[0005] [Figure 1] FIG. 1 depicts the study scheme of a Phase 2, multicenter, open-label study to evaluate the efficacy and safety of erdafitinib in subjects with metastatic or surgically unresectable urothelial carcinoma harboring selected FGFR (fibroblast growth factor receptor) genetic alterations (FGFR translocations or mutations). [Diagram 2] Figure 2 represents a waterfall plot of the maximum percentage reduction from baseline in the sum of target lesion diameters among patients treated with the 8 mg continuous erdafitinib regimen (regimen 3 of the phase 2 study (Figure 1)). M, FGFR mutation; T, FGFR translocation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0006] The present invention limits potential toxicities while also providing a method for treating already in the first cycle of treatment (e.g., Within the first 28 days of treatment or the first 21 days of treatment with daily continuous dosing and further treatment cycles (e.g., 28 days with continuous daily dosing). / cycle or 21 days / cycle) to maximize erdafitinib exposure Treatment of cancer with dafitinib is provided.

[0007] The present invention maximizes erdafitinib exposure and provides treatment for subjects in need of erdafitinib. , target serum phosphate range, specifically 5.5 mg / dL to 7. Less than 5.5 mg / dL or 5.5 mg / dL to 9 mg / dL, inclusive Erdafitinib's cancer treatment, which rapidly reduces phosphate toxicity, Provide treatment.

[0008] Erdafitinib or N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl) -N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl ]ethane-1,2-diamine inhibits pan-fibroblast growth factor receptors (FGFR 1, 2, 3, 4) ) tyrosine kinase inhibitor.

[0009] The chemical structure of erdafitinib is [ka] It is.

[0010] Serum phosphate concentration predicts FGFR target engagement by erdafitinib Serum phosphate concentration may represent an on-target pharmacodynamic marker indicative of the activity of the target enzyme. However, it is likely to increase with engagement. In order to prevent or control phosphateuria, serum phosphate concentrations must be monitored.

[0011] A higher proportion of patients had eldafi It was found to be responsive to tinib treatment.

[0012] In one embodiment, the proportion of patients experiencing an objective response rate is at least 15%, 20%, 25%, 30%, 35%, 40%, or 45% , 50%, 55%, 60%, 65%, or more than 65%.

[0013] In one embodiment, exposure to erdafitinib may be at least 100% effective, depending on the type of cancer. At least 15%, 20%, 25%, 30%, 35%, 40%, or 4 Those that give an objective response rate of 5%, 50%, 55%, 60%, 65%, or greater than 65%. That is why.

[0014] In one embodiment, the serum phosphate concentration of the cancer patient is 5-fold lower upon exposure to erdafitinib. .5 mg / dL or higher, specifically 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL Range of less than 5.5 mg / dL or range of 5.5 mg / dL to 9 mg / dL (including 5.5 mg / dL) and, depending on the type of cancer, at least 15%, or 20%, or 25%, or 30% , or 35%, or 40%, or 45%, 50%, 55%, 60%, 65%, or 65% It gives an objective response rate of ultra high.

[0015] In one embodiment, the method of treating cancer described herein or the method of treating cancer described herein Use for the manufacture of a medicament for the treatment of cancer or for use in the treatment of cancer as described herein. Erdafitinib for the treatment of rheumatoid arthritis is at least 15%, 20%, 25%, or 30% , or 35%, or 40%, or 45%, 50%, 55%, 60%, 65%, or 65% It gives an objective response rate of ultra high.

[0016] In one embodiment, the cancer is urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, Urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable The method of treating a cancer as described herein, wherein the cancer is a urothelial cancer, or for use in the treatment of cancer as described herein. Erdafitinib for EGFR-associated leukemia provides an objective response rate of at least 40%, specifically, approximately 40%. %, about 41%, about 42%, about 43%, about 44%, about 45% %, about 46%, about 47%, about 48%, about 49%, about 50% Specifically, the objective response rate is in the range of 40% to 50%, or 40% to 45%. range, or between 42% and 45%.

[0017] In one embodiment, urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, in particular urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable urinary tract cancer In patients with epithelial cancer, erdafitinib according to the dosing regimen disclosed herein The objective response rate upon exposure to is at least 40%, specifically about 40%, and is approximately 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, and about 50%. Specifically, the objective response rate was in the range of 40% to 50%, or 40% to 45%, or 4. The range is 2% to 45%.

[0018] In one embodiment, the method of treating cancer described herein or the method of treating cancer described herein Use for the manufacture of a medicament for the treatment of cancer or for use in the treatment of cancer as described herein. Erdafitinib for at least 4 months, or at least 5 months, or at least also provided a median duration of response of 6 months, or at least 7 months.

[0019] In one embodiment, the cancer is urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, Urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable The method of treating a cancer as described herein, wherein the cancer is a urothelial cancer, or for use in the treatment of cancer as described herein. Erdafitinib for at least 4 months, or at least 5 months, or at least Provide a median duration of response of 6 months, or at least 7 months, or about 4 months, or about 5 months, or months, or about 6 months, or about 7 months. Specifically, the median duration of response is 4 months to 7 months. The range is.

[0020] In one embodiment, urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, in particular urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable urinary tract cancer In patients with epithelial cancer, erdafitinib according to the dosing regimen disclosed herein The median duration of response upon exposure to IFN-α was at least 4 months, or at least 5 months, or 6 months, or at least 7 months, or about 4 months, or about 5 months, or about The median duration of response ranged from 4 to 7 months. do.

[0021] In one embodiment, the method of treating cancer described herein or the method of treating cancer described herein Use for the manufacture of a medicament for the treatment of cancer or for use in the treatment of cancer as described herein. Erdafitinib for at least 4 months, or at least 5 months, or at least also confers a median progression-free survival of 6 months, or at least 7 months.

[0022] In one embodiment, the cancer is urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, Urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable The method of treating a cancer as described herein, wherein the cancer is a urothelial cancer, or for use in the treatment of cancer as described herein. Erdafitinib for at least 4 months, or at least 5 months, or at least Provide a median progression-free survival of 6 months, or at least 7 months, or approximately 4 months, or about 5 months, or about 6 months, or about 7 months. Specifically, the median progression-free survival ranges from 4 to 7 months.

[0023] In one embodiment, urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, in particular urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable urinary tract cancer In patients with epithelial cancer, erdafitinib according to the dosing regimen disclosed herein Median progression-free survival at the time of exposure to is at least 4 months, or at least 5 months, or At least 6 months, or at least 7 months, or about 4 months, or about 5 months, or about 6 months, or about 7 months. Specifically, the median progression-free survival is 4 to 7 months. It is a range of months.

[0024] The method of treating cancer as described herein or the medicament for treating cancer as described herein Use of Erdafiche for the manufacture of a product or for the treatment of cancer as described herein. Median time to response to nib e) is very short. In one embodiment, the median time to response is less than 2 months, specifically Generally, it is less than 1.5 months, and more specifically, around 1.4 months.

[0025] In one embodiment, the cancer is urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, Urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable The method of treating a cancer as described herein, wherein the cancer is a urothelial cancer, or for use in the treatment of cancer as described herein. Erdafitinib for rheumatoid arthritis has a time to response of less than 2 months, specifically less than 1.5 months. The median value is given, specifically around 1.4 months.

[0026] In one embodiment, urothelial carcinoma, metastatic or surgically unresectable urothelial carcinoma, in particular urothelial carcinoma with selected FGFR gene alterations, metastatic or surgically unresectable urinary tract cancer In patients with epithelial cancer, erdafitinib according to the dosing regimen disclosed herein The median time to response upon exposure to rituximab was less than 2 months, specifically less than 1.5 months. , specifically around 1.4 months.

[0027] Surprisingly, the treatment of cancers described herein, in particular urothelial cancer, metastatic or surgical Unresectable urothelial carcinoma, specifically urothelial carcinoma with selected FGFR genetic alterations; Response to treatment of metastatic or surgically unresectable urothelial carcinoma is unclear in patients, e.g., chemotherapy-naïve. Patients who have not received chemotherapy, specifically those who are ineligible for cisplatin and have not received one prior line of chemotherapy Patients with disease progression after chemotherapy or disease progression after 2 or more prior lines of chemotherapy It was found that the effect of serotonin-dependent creatinine (SEQ ID NO: 1) on the progression of glaucoma was independent of the number of lines of prior therapy that patients with SEQ ID NO: 1 had received. In this study, the response to treatment was evaluated in patients with different numbers of prior lines of therapy, e.g. chemotherapy-naïve patients, specifically those who are not suitable for cisplatin and those who have not received chemotherapy before Patients with disease progression after first-line chemotherapy or after two or more prior lines of chemotherapy In one embodiment, the prior line of chemotherapy is similar to that of patients with disease progression. Patients with, e.g., disease progression after one prior line of chemotherapy or patients with, Response to cancer treatment by patients who have had disease progression after two or more lines of chemotherapy No worse than for chemotherapy-naive patients.

[0028] Serum phosphate concentrations above 7 mg / dL, specifically above 9 mg / dL, are a sign of temporary erudation. This may be a reason to discontinue erdafitinib treatment or adjust the erdafitinib dose (reduce the dose). It was found that:

[0029] In one embodiment, temporary erdafitinib discontinuation is performed until serum phosphate levels return to 5. This represents discontinuation of erdafitinib administration until the serum concentration reaches <5 mg / dL.

[0030] In one embodiment, temporary erdafitinib interruption is initiated when serum phosphate levels return to 7 m This represents the interruption of erdafitinib administration until the serum creatinine concentration reaches < 10 g / dL.

[0031] Effective and safe treatment with erdafitinib has demonstrated that serum phosphate concentrations are >5.5 mg / mL. Between 5.5 mg / dL and less than 7 mg / dL, or between 5.5 mg / dL and less than 5 mg / dL, Eldaf is administered at therapeutically effective doses ranging from 0.5 mg / dL to 9 mg / dL. It was found that administering ritinib was effective.

[0032] Serum phosphate concentration can be measured using, for example, the ab65622 Phosphate Assay Kit. This can be measured using commercially available kits such as Colorimetric (Abcam).

[0033] Daily, preferably once a day, continuous (unless the context indicates otherwise, daily throughout treatment) No discontinuation, no intermittent dosing) Administration of 8 mg of erdafitinib resulted in no potential drug-related Eldafi Subjects who require tinib treatment, specifically cancer patients, should have a serum phosphate concentration of 5.5 mg / dL or higher. It has been found that the likelihood of reaching or exceeding the threshold is increased.

[0034] With continuous daily administration of 8 mg of erdafitinib, preferably once daily, 5. 5 mg / dL serum phosphate concentration in the first cycle of erdafitinib treatment (e.g., It has been found that the 28 days or first 21 days of the study can be achieved within 28 days of the study. Erdafitinib was administered at a continuous dose of 8 mg once daily. Subjects in need, specifically cancer patients, were provided with a full course of treatment during the first cycle of erdafitinib treatment. Early in the treatment (e.g., on day 14 ± 2 of treatment), serum phosphate concentration of 5.5 mg / dL Increased likelihood of reaching or exceeding these thresholds, leading to treatment interruption or This has been shown to maximize effective treatment while minimizing the need for dose reduction. It was served.

[0035] In one embodiment, a subject in need of erdafitinib treatment, particularly a cancer patient, Serum phosphate concentrations are monitored.

[0036] In one embodiment, a subject in need of erdafitinib treatment, particularly a cancer patient, Subjects in whom serum phosphate concentrations are monitored and who require erdafitinib treatment, specifically subjects with cancer Early onset symptoms associated with FGFR inhibitors in general or erdafitinib specifically as presented by patients Early onset toxicity will be monitored.

[0037] In one embodiment, the early stages associated with FGFR inhibitors in general or erdafitinib specifically are Phase toxicities included grade 3 or greater xerostomia or stomatitis / mucositis, dry skin, dry Nail toxicity (or Grade 2 if lasting longer than 1 week) or ocular toxicity (corneal Uveitis, central serious retinopathy Early developmental toxicity may be a reason to discontinue treatment or reduce dose. This is at the discretion of the physician and may depend on the patient's condition.

[0038] In one embodiment, the early developmental toxicity or FGFR inhibitors generally described herein Early developmental toxicity, particularly associated with erdafitinib, is usually grade 3 or higher. Possible side effects include: stomatitis / mucositis, dry skin, dry eyes, nail toxicity or specific eye Toxicity (keratitis, or retinopathy also called central serous retinopathy, retinal detachment, retinal edema, retinal pigment epithelial detachment, retinal choroiditis) or FGFR inhibitors in general or in particular FGFR inhibition is associated with other significant toxicities that appear to be differentially related to erdafitinib Clinically significant toxicities considered to be drug-related or erdafitinib-specific Early developmental toxicity may be a reason to discontinue treatment or reduce the dose. It may depend on the patient's condition.

[0039] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, Serum phosphate concentration between 5.5 mg / dL and less than 7 mg / dL, including 5.5 mg / dL In one embodiment, the method comprises administering an amount of erdafitinib in a range of In the present study, the amount of erdafitinib was 8 mg, specifically 8 mg administered continuously daily. The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, in particular a cancer patient. In patients with erdafitinib, serum phosphate concentrations were increased within the first cycle of treatment (treatment cycle The period may be set, for example, for the first 28 days of dosing or the first 21 days of dosing, serum phosphate Concentrations were measured on or about the 28th day, or on or about the 21st day, or on or about the 14th day after administration. (evaluated at or before or after) 5.5mg / dL to 7mg / dL, including 5.5mg / dL The present invention relates to methods comprising administering erdafitinib in an amount such that the therapeutic efficacy is in the range of less than 100 mg / kg. In one embodiment, the amount of erdafitinib is 8 mg, specifically administered continuously every day. The dose is 8 mg.

[0040] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, Serum phosphate concentration between 5.5 mg / dL and 9 mg / dL, including 5.5 mg / dL In one embodiment, the method comprises administering an amount of erdafitinib in a range of In the present study, the amount of erdafitinib was 8 mg, specifically 8 mg administered continuously daily. The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, in particular a cancer patient. In patients with erdafitinib, serum phosphate concentrations were increased within the first cycle of treatment (treatment cycle The period may be set, for example, for the first 28 days of dosing or the first 21 days of dosing, serum phosphate Concentrations were measured on or about the 28th day, or on or about the 21st day, or on or about the 14th day after administration. (evaluated at or before or after 5.5 mg / dL to 9 mg / dL, including 5.5 mg / dL) The present invention relates to a method comprising administering an amount of erdafitinib such that the following range is reached: In one embodiment, the amount of erdafitinib is 8 mg, specifically administered continuously every day. The dose is 8 mg.

[0041] The present invention relates to a method for treating a patient having a serum phosphate concentration of 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL. 1. The method of claim 1, wherein the amount of the compound is in the range of 0.1 mg / dL or less. The present invention relates to the use of erdafitinib in patients with rhabdomyolysis, in which serum phosphate levels are increased after administration of erdafitinib. Within one cycle (treatment cycle duration may be, for example, the first 28 days of administration or the first The serum phosphate concentration was measured on or around the 28th day of administration or on the 21st day. or on or about the 14th day) including 5.5 mg / dL. Medications for the treatment of cancer in amounts that reach a range of 5 mg / dL to less than 7 mg / dL Use of erdafitinib for the manufacture of a medicament. The amount of tinib is 8 mg, specifically 8 mg administered continuously daily.

[0042] The present invention relates to a method for treating a patient having a serum phosphate concentration of 5.5 mg / dL to 9 mg / dL, including 5.5 mg / dL. 1. The method of claim 1, wherein the amount of the compound is in the range of 0.1 mg / dL or less. The present invention relates to the use of erdafitinib in patients with rhabdomyolysis, in which serum phosphate levels are increased after administration of erdafitinib. Within one cycle (treatment cycle duration may be, for example, the first 28 days of administration or the first The serum phosphate concentration was measured on or around the 28th day of administration or on the 21st day. or on or about the 14th day) including 5.5 mg / dL. Medications for the treatment of cancer in amounts that reach a range of 5 mg / dL to 9 mg / dL or less Use of erdafitinib for the manufacture of a medicament. The amount of tinib is 8 mg, specifically 8 mg administered continuously daily.

[0043] The present invention relates to a method for treating a patient having a serum phosphate concentration of 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL. Erdafitinib is administered in amounts such that the blood glucose level is in the range of less than 1 / dL for use in the treatment of cancer. The present invention relates to a method for treating erdafitinib for the treatment of rheumatoid arthritis. Within the first cycle of administration (treatment cycle duration may be, for example, the first 28 days of administration or During the first 21 days of treatment, serum phosphate concentrations were measured on or about the 28th day of treatment, or (evaluated on or about the 21st day or on or about the 14th day) 5.5 mg / dL Contains erudafinitin in amounts that reach a range of 5.5 mg / dL to less than 7 mg / dL In one embodiment, the present invention relates to erdafitinib for use in the treatment of cancer, in which a medicament is administered. In this case, the amount of erdafitinib is 8 mg, specifically 8 mg administered continuously daily. do.

[0044] The present invention relates to a method for treating a patient having a serum phosphate concentration of 5.5 mg / dL to 9 mg / dL, including 5.5 mg / dL. Erdafitinib is administered in amounts such that the blood glucose level is in the range of 0.01 mg / dL or less for use in the treatment of cancer. The present invention relates to a method for treating erdafitinib for the treatment of rheumatoid arthritis. Within the first cycle of administration (treatment cycle duration may be, for example, the first 28 days of administration or During the first 21 days of treatment, serum phosphate concentrations were measured on or about the 28th day of treatment, or (evaluated on or about the 21st day or on or about the 14th day) 5.5 mg / dL In amounts that will reach a range of 5.5 mg / dL to 9 mg / dL or less, In one embodiment, the present invention relates to erdafitinib for use in the treatment of cancer, in which a medicament is administered. In this case, the amount of erdafitinib is 8 mg, specifically 8 mg administered continuously daily. do.

[0045] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. Dose adjustments can be made based on serum phosphate concentrations without the presence of toxicity. It can be observed about this.

[0046] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer, comprising: The drug contains erdafitinib in an amount of 8 mg, and the drug is administered daily, specifically once daily. of erdafitinib for the manufacture of a medicament for the treatment of cancer, which is for continuous administration. Dosage adjustments can be made based on serum phosphate concentrations in the absence of toxicity. It can be observed about this.

[0047] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. The present invention relates to erdafitinib for use in the treatment of cancer. Based on the acid salt concentration, observations can be made regarding the absence of toxicity.

[0048] During treatment with erdafitinib at a dose of 8 mg daily, preferably once daily, for continuous Serum phosphate levels can be monitored. If serum phosphate levels are below 5.5 mg / dL, In this case, the dose of erdafitinib is increased and administered daily, preferably once a day, for 9 consecutive days. g. In one embodiment, the serum phosphate level to determine whether to titrate is The concentration of erdafitinib was measured on the treatment day during the first cycle of erdafitinib treatment, specifically It is measured on day 14 ± 2 of Tinib administration, more specifically on day 14.

[0049] During treatment with erdafitinib at a dose of 8 mg daily, preferably once daily, for continuous Serum phosphate levels can be monitored. If serum phosphate levels are less than 7 mg / dL or is in the range of 7 mg / dL to 9 mg / dL, inclusive, or is less than or equal to 9 mg / dL. If the blood glucose level is below 1000 mg / kg, the dose of erdafitinib should be increased to once daily, preferably once a day. In one embodiment, the dose can be titrated up to 9 mg once every 10 minutes. Serum phosphate concentrations for erdafitinib were measured specifically on the treatment day during the first cycle of treatment. Typically, the patient is measured on day 14 ± 2 of erdafitinib administration, and more specifically on day 14. .

[0050] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. In one embodiment, the method comprises the step of: Serum phosphate concentrations to determine whether the first cycle of erdafitinib treatment on treatment days between, specifically on day 14 ± 2 of erdafitinib administration, and more specifically Measured on the 14th day.

[0051] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once daily, the serum phosphate concentration of the cancer patient is monitored. In one embodiment, the present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer. In patients with erdafitinib treatment, serum phosphate concentration was determined to determine whether to titrate. On treatment days during the first cycle of treatment, specifically on days 14 ± 2 of erdafitinib administration. , more specifically measured on day 14.

[0052] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. and monitoring the serum phosphate concentration of the cancer patient. In one embodiment, the serum lipase (LLP) is administered to determine whether to titrate. The phosphate concentration was measured on the treatment day during the first cycle of erdafitinib treatment, specifically on the It is measured on day 14±2 of dafitinib administration, more specifically on day 14.

[0053] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. , a method comprising monitoring a subject's serum phosphate concentration, If the daily dose of erdafitinib is less than 100 g / dL, the daily dose of erdafitinib administered continuously, preferably The dose is increased to 9 mg once daily. Serum phosphate concentration is 5.5 mg / dL. If the range was between 5 mg / dL and less than 7 mg / dL, subjects were to receive 8 mg of continuous daily If serum phosphate levels are 7 mg / dL or higher, treatment should be temporarily discontinued. Specifically, erdafitinib treatment was discontinued, and serum phosphate levels were again reduced to <7 mg / dL. or the daily continuous dose is adjusted to less than 8 mg, specifically Treatment is temporarily suspended, specifically until serum phosphate is <5.5 mg / dL In one embodiment, serum phosphate concentration is measured in the first cycle of erdafitinib treatment. On treatment days during the course of treatment, more specifically on day 14 ± 2 of erdafitinib administration In one embodiment, serum phosphate concentration is specifically measured on day 14. On day ±2, more specifically on day 14, 7 mg / dL or more, specifically 7 mg / dL If serum phosphate is between 7 mg / dL and 9 mg / dL, the serum phosphate level is 5.5 Treatment was temporarily interrupted until serum erythrocyte sedimentation was < 100 mg / dL, and then erdafitinib treatment was discontinued. Daily, specifically, resumed at 8 mg continuously once daily.

[0054] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0055] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. , a method comprising monitoring a serum phosphate concentration in a subject, If the daily dose of erdafitinib is less than 1000 mg / dL, the daily dose of erdafitinib administered continuously, preferably 1000 mg / dL, is The dose is increased to 9 mg. Serum phosphate levels are between 7 mg / dL and If the serum glucose level is within the range of 0.01 mg / dL or less, a phosphate binder such as sevelamer should be used in parallel. Treatment with erdafitinib is optionally initiated, while continuous daily erdafitinib is administered. The amount, preferably a once daily dose, is increased to 9 mg. Combination therapy with phosphate binders such as Lamar is started. Serum phosphate concentration > 9 mg / dL If serum LDL cholesterol rises to 100 mg / kg / day, treatment should be temporarily interrupted. The drug was discontinued until serum phosphate was again <7 mg / dL. Once full, each successive dose is adjusted to the same or a lower daily dose. In the event of persistent serum phosphate concentrations of 10 mg / dL or greater for any length of time, treatment should be permanently discontinued. Specifically, erdafitinib treatment is permanently discontinued. The salt concentration was determined on the treatment day during the first cycle of erdafitinib treatment, specifically, on erdafitinib. The measurement is performed on day 14 ± 2 of administration of ritinib, more specifically on day 14. If serum phosphate is >9 mg / dL, serum phosphate is >7 mg / dL. Treatment is temporarily interrupted until the blood glucose level is below 1 L, and then erdafitinib treatment is resumed daily. Specifically, the dose is resumed at 8 mg continuously once daily. Serum phosphate concentrations during dafitinib administration can be controlled according to Table 4.

[0056] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. , monitoring of the subject's serum phosphate concentration and FGFR inhibitors in general or specifically erdaphytin The present invention relates to a method for monitoring early developmental toxicity exhibited by subjects in association with serum If the phosphate concentration is less than 5.5 mg / dL and no early developmental toxicity is demonstrated, The daily dose of erdafitinib, preferably given once daily, should be increased to 9 mg. Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL. If the mean mean serum creatinine concentration is within the range of 0.01 mg / kg and no early developmental toxicity is noted, subjects should be Treatment should remain continuous. If serum phosphate is 7 mg / dL or higher, treatment should be discontinued. Erdafitinib treatment was discontinued until serum phosphate levels were reduced to 7 mg / dL or higher. The daily continuous dose should be adjusted to less than 8 mg or discontinued until the daily continuous dose is less than 8 mg. Generally, treatment is temporary, specifically, serum phosphate levels below 5.5 mg / dL. In one embodiment, serum phosphate concentrations are discontinued until the end of erdafitinib treatment. On treatment days during the first cycle, specifically on days 14 ± 2 of erdafitinib administration, More specifically, it is measured on day 14. In one embodiment, the serum phosphate concentration is 7 mg / mL or lower. If serum phosphate is less than 5.5 mg / dL, treatment should be temporary until serum phosphate is less than 5.5 mg / dL. Erdafitinib treatment was then discontinued daily, specifically once daily, for 8 consecutive days. It is resumed with mg.

[0057] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0058] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 8 mg of erdafitinib continuously, once daily. , monitoring of the subject's serum phosphate concentration and FGFR inhibitors in general or specifically erdaphytin The present invention relates to a method for monitoring early developmental toxicity exhibited by subjects in association with serum If phosphate concentrations are less than 7 mg / dL and no early developmental toxicity is demonstrated, The daily dose of erdafitinib administered to Serum phosphate concentration in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL If there is evidence of early developmental toxicity, then parallel use of phosphorylation inhibitors such as sevelamer may be warranted. Erdafitinib administered continuously while adsorbent therapy is optionally initiated The daily amount, preferably a once daily amount, of is increased to 9 mg. If serum phosphate concentration is >9 mg / kg, combination therapy with a phosphate binder such as sevelamer is started. If the serum creatinine concentration rises above 1000 mg / kg, treatment should be temporarily interrupted. The treatment was discontinued until serum phosphate was again < 7 mg / dL, and serum phosphate was 7 mg / If the daily dose falls below 100 dL, the subsequent daily doses are adjusted to the same or lower daily dose. In an embodiment, the serum phosphate concentration is measured during the first cycle of erdafitinib treatment. On the day of treatment, specifically on day 14 ± 2 of erdafitinib administration, more specifically on day 14 In one embodiment, if the serum phosphate concentration is greater than 9 mg / dL: Treatment was temporarily suspended until serum phosphate levels were <7 mg / dL, then endothelial cell death was prevented. Rudafitinib treatment is resumed daily, specifically at 8 mg continuously once daily.

[0059] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0060] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 9 mg of erdafitinib continuously, once daily. , including monitoring the subjects' serum phosphate levels, and administering a continuous 8 mg / day The subject's serum phosphate concentration is 5.5 while receiving erdafitinib In one embodiment, if the blood glucose level is less than 100 mg / dL, 9 mg is administered to the subject. In this study, serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment, Specifically, the measurements were taken on day 14 ± 2 of erdafitinib administration, and more specifically on day 14. do.

[0061] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0062] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 9 mg of erdafitinib continuously, once daily. The patient was receiving continuous treatment with erdafitinib at a dose of 8 mg once daily. If, during the course of the study, the subject has a serum phosphate concentration of less than 7 mg / dL, or If the salt concentration is in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL, g is administered to a subject, the serum phosphate concentration being 7 mg / dL or more. dL to 9 mg / dL, in combination with phosphate binders such as sevelamer In one embodiment, a combination therapy with a phosphate binder, such as sevelamer, may be initiated. In one embodiment, serum phosphate levels are monitored after erdafitinib administration. The measurements are taken on day 14 ± 2 of administration, specifically on day 14.

[0063] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0064] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 9 mg of erdafitinib continuously, once daily. The patient was receiving continuous treatment with erdafitinib at a dose of 8 mg once daily. During the course of treatment, the subject has a serum phosphate concentration of less than 5.5 mg / dL and is If no sexual activity is indicated, 9 mg is administered to the subject. Serum phosphate concentrations were specifically measured on treatment days during the first cycle of erdafitinib treatment. Typically, the patient is measured on day 14 ± 2 of erdafitinib administration, and more specifically on day 14. .

[0065] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0066] The present invention relates to a method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, This involves administering 9 mg of erdafitinib continuously, once daily. The patient was receiving continuous treatment with erdafitinib at a dose of 8 mg once daily. If the patient has a serum phosphate concentration of less than 7 mg / dL during Concentration is in the range of 7 mg / dL to 9 mg / dL (including 7 mg / dL) and early onset If no biotoxicity is observed, 9 mg is administered to a cancer patient. Serum phosphate Concentration is in the range of 7 mg / dL to 9 mg / dL (including 7 mg / dL) and early onset If no biotoxicity is observed, combination therapy with a phosphate binder, such as sevelamer, may be initiated. In one embodiment, combination therapy with a phosphate binder, such as sevelamer, is initiated. In one embodiment, serum phosphate concentration is measured after the first cycle of erdafitinib treatment. On treatment days between the two trials, specifically on day 14 ± 2 of erdafitinib administration, is measured on day 14.

[0067] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0068] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once daily, serum phosphate levels in cancer patients were monitored, and serum phosphate If the salt concentration is less than 5.5 mg / dL, daily, specifically once a day, continuous administration is recommended. The amount of erdafitinib in the drug product for the treatment of cancer in cancer patients is increased to 9 mg. Use of erdafitinib for the manufacture of a medicinal product for treating patients with a serum phosphate concentration of 5.5m If the range is between 5.5 mg / dL and less than 7 mg / dL, including 8 mg / dL, the patient g daily for continuous therapy. If serum phosphate levels are 7 mg / dL or higher, Treatment was temporarily interrupted, specifically erdafitinib treatment, until serum phosphate levels returned to normal. Discontinued until < 7 mg / dL or adjusted to < 8 mg daily continuous dose Specifically, the treatment is temporary, specifically, to reduce serum phosphate levels to 5.5 mg / dL. In one embodiment, the serum phosphate concentration is discontinued until it is less than 0.05 mg / kg. On treatment days during the first cycle of erdafitinib treatment, specifically on day 14 of erdafitinib administration ± In one embodiment, serum phosphate concentration is measured on day 2, more specifically on day 14. If serum phosphate is 7 mg / dL or higher, treat until serum phosphate is <5.5 mg / dL The treatment is temporarily interrupted, and then erdafitinib treatment is resumed daily, specifically once daily. Resume at 8 mg continuously.

[0069] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0070] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once daily, serum phosphate levels in cancer patients were monitored, and serum phosphate If the salt concentration is less than 7 mg / dL, daily, specifically once a day, for continuous administration The amount of erdafitinib in the drug will be increased to 9 mg, a medical product for the treatment of cancer in cancer patients. Use of Erdafitinib for the manufacture of a drug. Serum phosphate concentration 7mg / dL If the range is between 7 mg / dL and 9 mg / dL, then in parallel, e.g., sevelam While treatment with phosphate binders such as phosphate binders is optionally initiated, daily, specifically once a day, The amount of erdafitinib for each successive administration is increased to 9 mg. In such cases, combination therapy with a phosphate binder, such as sevelamer, is initiated. If the serum creatinine rises to more than 9 mg / dL, treatment should be temporarily interrupted, specifically with erdafichinib. Treatment was discontinued until serum phosphate was again <7 mg / dL. If the daily dose falls below 7 mg / dL, the daily successive doses should be adjusted to the same or lower daily dose. In one embodiment, serum phosphate concentration is measured in the first cycle of erdafitinib treatment. On treatment days during the course of treatment, more specifically on day 14 ± 2 of erdafitinib administration In one embodiment, serum phosphate levels greater than 9 mg / dL are measured on day 14. In some cases, treatment is temporarily suspended until serum phosphate levels are less than 7 mg / dL. Erdafitinib treatment was then resumed daily, specifically at 8 mg continuously once daily. can be.

[0071] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0072] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically, once a day. Because of the continuous administration once a day, the serum phosphate levels of cancer patients were monitored and As shown, early developmental toxicity associated with FGFR inhibitors in general and erdafitinib specifically Patients were monitored to determine whether serum phosphate levels were below 5.5 mg / dL and there was no evidence of early developmental toxicity. Unless otherwise indicated, Eldaf in medicines for continuous administration daily, specifically once a day The amount of imipramine is increased to 9 mg, Regarding the use of rudafitinib. Serum phosphate concentration is 5.5 mg / dL or less. If the serum creatinine concentration is in the range of 0.1 mg / dL to < 7 mg / dL and no early developmental toxicity is observed, Patients should continue to receive 8 mg daily for continuous therapy. In some cases, treatment was temporarily interrupted and erdafitinib treatment was discontinued, specifically after serum phosphate The drug is discontinued until concentrations are again <7 mg / dL or continuous daily doses are increased to 8 mg / dL. g, specifically, treatment is temporarily adjusted to serum phosphate levels below 5. In one embodiment, serum phosphate is discontinued until it is less than 5 mg / dL. On treatment days during the first cycle of erdafitinib treatment, specifically erdafitinib administration In one embodiment, serum Serum phosphate concentration < 5.5 mg / dL if phosphate concentration is ≥ 7 mg / dL Treatment is then temporarily suspended until erdafitinib treatment is resumed daily, specifically is resumed at a continuous dose of 8 mg once daily.

[0073] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0074] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically, once a day. Because of the continuous administration once a day, the serum phosphate levels of cancer patients were monitored and As shown, early developmental toxicity associated with FGFR inhibitors in general and erdafitinib specifically were monitored and serum phosphate concentrations were <7 mg / dL and no early developmental toxicity was noted. If not possible, erdaphytin in medicines for continuous administration daily, specifically once a day The amount of nibs is increased to 9 mg, Erda for the manufacture of medicines for the treatment of cancer in cancer patients Use of phytinib. Serum phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL. If the concentration is in the range of 0.5 mg / dL or less and no early developmental toxicity is observed, Treatment with phosphate binders such as sevelamer is optionally initiated, while specific The dose of erdafitinib for continuous administration will be increased to 9 mg once daily. In some embodiments, combination therapy with a phosphate binder, such as sevelamer, is initiated. If phosphate levels rise above 9 mg / dL, treatment should be temporarily interrupted and specifically Dafitinib treatment was interrupted until serum phosphate levels were again <7 mg / dL. Once serum phosphate falls below 7 mg / dL, the daily continuous dose should be the same or lower. In one embodiment, the serum phosphate concentration is adjusted to the daily dose after erdafitinib treatment. On treatment days during the first cycle of More specifically, it is measured on day 14. In one embodiment, the serum phosphate concentration is 9 mg If serum phosphate is > 7 mg / dL, treatment is temporary until serum phosphate is < 7 mg / dL. The erdafitinib treatment is then discontinued and resumed daily, specifically once daily, for 8 consecutive minutes. It is resumed with g.

[0075] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0076] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 9 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once a day, specifically, 8 mg of eltrombopagus per day While undergoing treatment with dafitinib, the patient's serum phosphate concentration was 5.5 mg / mL. dL, the drug is administered to the cancer patient, In one embodiment, the present invention relates to the use of erdafitinib for the manufacture of a pharmaceutical composition for treating or preventing atopic dermatitis. The dose was determined on the treatment day during the first cycle of erdafitinib treatment, specifically on the day of erdafitinib The measurement is performed on day 14 ± 2 of administration of the antibody, more specifically on day 14.

[0077] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0078] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 9 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once a day, specifically, 8 mg of eltrombopagus per day While undergoing treatment with dafitinib, the patient's serum phosphate level was 7 mg / dL or serum phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL dL or less, the drug is administered to a cancer patient, Use of Erdafitinib for the manufacture of a drug. Serum phosphate concentration 7mg / dL If the range is between 7 mg / dL and 9 mg / dL, for example, sevelamer, In one embodiment, combination therapy with a lysozyme adsorbent, such as sevelamer, may be initiated. In one embodiment, the serum phosphate concentration is increased to 100 mg / kg / day. On treatment days during the first cycle of dafitinib treatment, specifically on the first day of erdafitinib administration Measurements are taken on day 4±2, more specifically on day 14.

[0079] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0080] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 9 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once a day, specifically, 8 mg of eltrombopagus per day While undergoing treatment with dafitinib, the patient's serum phosphate concentration was 5.5 mg / mL. If the dose is less than 100 mg / kg and no early developmental toxicity is demonstrated, the drug may be administered to cancer patients. The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. In an embodiment, the serum phosphate concentration is measured during the first cycle of erdafitinib treatment. On the day of treatment, specifically on day 14 ± 2 of erdafitinib administration, more specifically on day 14 Measured by eye.

[0081] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0082] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. and the drug product contains erdafitinib in an amount of 9 mg, and the drug product is administered daily, specifically, once a day. For continuous administration once a day, specifically, 8 mg of eltrombopagus per day While undergoing treatment with dafitinib, the patient's serum phosphate level was 7 mg / dL or serum phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL If the drug is administered to cancer patients, and the drug shows no early developmental toxicity, The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. Serum phosphate concentration in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL and no early developmental toxicity is demonstrated, Combination therapy may be initiated. In one embodiment, combination therapy with a phosphate binder, such as sevelamer, Combination therapy is initiated. In one embodiment, serum phosphate levels are increased by erdafitinib On treatment days during the first cycle of treatment, specifically day 14 ± 2 of erdafitinib administration , and more specifically on day 14.

[0083] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0084] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. and serum phosphate levels in cancer patients were monitored, and serum phosphate levels below 5.5 mg / dL were When the amount of erdafitinib administered continuously every day, preferably once a day, is 9 erdafitinib for use in treating cancer in a cancer patient, the serum Phosphate concentration in the range of 5.5 mg / dL to less than 7 mg / dL, including 5.5 mg / dL In some cases, patients remain on continuous treatment with 8 mg daily. / dL or higher, treatment is temporarily suspended, specifically, erdafitinib treatment is The drug is discontinued until serum phosphate levels are again <7 mg / dL or is continued daily. The dosage is adjusted to less than 8 mg, and treatment is specifically initiated when serum phosphate levels are below 5 In one embodiment, serum phosphate is temporarily discontinued until serum phosphate is below 0.5 mg / dL. The concentration of erdafitinib was measured on the treatment day during the first cycle of erdafitinib treatment, specifically The measurement is performed on day 14 ± 2 of administration of tinib, more specifically on day 14. If serum phosphate concentration is 7 mg / dL or higher, serum phosphate concentration is 5.5 mg / dL or higher. Treatment was temporarily interrupted until blood glucose levels were below 1 / dL, and then erdafitinib treatment was discontinued daily. , specifically, resumed at a continuous dose of 8 mg once daily.

[0085] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0086] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. The serum phosphate levels of cancer patients were monitored, and if serum phosphate levels were less than 7 mg / dL, or serum phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL. Erdafitinib administered continuously daily, preferably once daily, if The amount of Erdafitinib for use in the treatment of cancer in a cancer patient is increased to 9 mg. Serum phosphate concentration in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL In some cases, combination therapy with a phosphate binder, such as sevelamer, may be initiated. In this case, combination therapy with a phosphate binder, such as sevelamer, is initiated. If the concentration rises above 9 mg / dL, treatment should be temporarily interrupted, specifically with Eldafi Tinib treatment was interrupted until serum phosphate concentrations were again <7 mg / dL, and serum phosphate Once the acid salts are below 7 mg / dL, the daily successive doses should be reduced to the same or lower daily dose. In one embodiment, the serum phosphate concentration is adjusted during the first period of erdafitinib treatment. More specifically, on treatment days between cycles, specifically on days 14 ± 2 of erdafitinib administration. Typically, the serum phosphate concentration is measured on day 14. If >7 mg / dL, treatment should be temporarily interrupted until serum phosphate is <7 mg / dL. Erdafitinib treatment was then resumed daily, specifically at 8 mg once daily. It will be opened.

[0087] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0088] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. The serum phosphate levels of cancer patients were monitored, and the FGFR inhibitor- Early developmental toxicity generally or specifically associated with erdafitinib will be monitored, and serum phosphate concentrations Daily is preferred if the serum creatinine concentration is less than 5.5 mg / dL and no early developmental toxicity is observed. The dose of erdafitinib is increased to 9 mg once daily for cancer patients. Erdafitinib for use in the treatment of cancer of the present invention, / dL and in the range of 5.5 mg / dL to less than 7 mg / dL, and early developmental toxicity If none are indicated, patients remain on continuous treatment with 8 mg daily. If the level is 7 mg / dL or higher, treatment should be temporarily suspended, specifically with erdafitinib. Treatment was discontinued until serum phosphate levels were again <7 mg / dL or daily. The continuous dose of is adjusted to less than 8 mg, and specifically, treatment is In one embodiment, blood salt concentration is temporarily suspended until the blood salt concentration is below 5.5 mg / dL. Serum phosphate concentrations were measured on treatment days during the first cycle of erdafitinib treatment, specifically The measurement is performed on day 14 ± 2 of erdafitinib administration, more specifically on day 14. In an embodiment, when the serum phosphate concentration is 7 mg / dL or more, the serum phosphate concentration is Treatment was temporarily interrupted until the serum glucose concentration was <5.5 mg / dL, and then erdafitinib treatment was started. Treatment is resumed daily, specifically at 8 mg continuously once daily.

[0089] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0090] The present invention relates to a method for treating erdafitinib, the method comprising administering erdafitinib in an amount of 8 mg daily, specifically once daily continuously. The serum phosphate levels of cancer patients were monitored, and the FGFR inhibitor- Early developmental toxicity generally or specifically associated with erdafitinib will be monitored, and serum phosphate concentrations is less than 7 mg / dL or if serum phosphate is 7 mg / dL or more dL to 9 mg / dL or less, daily, preferably once daily The amount of erdafitinib administered will be increased to 9 mg for use in treating cancer in patients with cancer. Regarding Erdafitinib: Serum phosphate concentrations between 7 mg / dL and 9 mg / dL, including 7 mg / dL In cases where the serum phosphate level is within the range of 0.5 mg / dL or less, combination therapy with phosphate binders such as sevelamer has been developed. In one embodiment, combination therapy with a phosphate binder, such as sevelamer, may be initiated. If serum phosphate rises above 9 mg / dL, treatment is temporarily discontinued. Specifically, erdafitinib treatment resulted in serum phosphate levels returning to <7 mg / dL. Once serum phosphate is below 7 mg / dL, the continuous daily dose is discontinued. In one embodiment, the serum phosphate concentration is adjusted to the same or lower daily dose. On treatment days during the first cycle of dafitinib treatment, specifically on the first day of erdafitinib administration In one embodiment, serum phosphorus is measured on day 4±2, more specifically on day 14. If serum phosphate is >9 mg / dL, treatment should be initiated to reduce serum phosphate to <7 mg / dL. Erdafitinib treatment is then discontinued daily, specifically once a day. The dose was resumed at 8 mg continuously for 10 min.

[0091] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0092] The present invention relates to erdafitinib for use in treating cancer in a cancer patient, the specific The above-mentioned patients were treated with erdafitinib at a continuous dose of 8 mg once daily. If the patient's serum phosphate concentration is less than 5.5 mg / dL, erdafitinib is administered at 9 mg / dL. g of 100 mg administered continuously daily, specifically once a day, for use in the treatment of cancer in cancer patients. In one embodiment, the serum phosphate concentration is On treatment days during the first cycle of dafitinib treatment, specifically on the first day of erdafitinib administration Measurements are taken on day 4±2, more specifically on day 14.

[0093] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0094] The present invention relates to erdafitinib for use in treating cancer in a cancer patient, the specific The above-mentioned patients were treated with erdafitinib at a continuous dose of 8 mg once daily. If the patient has a serum phosphate concentration less than 7 mg / dL or if the serum phosphate concentration is less than 7 mg / dL, If the serum plasma glucose level is within the range of 7 mg / dL to 9 mg / dL, including erdafitinib, It is used to treat cancer in cancer patients, administered continuously daily, specifically once a day, in an amount of 9 mg. The present invention relates to erdafitinib for use in patients with a serum phosphate concentration of 7 mg / dL or / dL to 9 mg / dL or less, e.g., with phosphate binders such as sevelamer Combination therapy may be initiated. In one embodiment, combination therapy with a phosphate binder, such as sevelamer, Combination therapy is initiated. In one embodiment, serum phosphate levels are increased by erdafitinib On treatment days during the first cycle of treatment, specifically day 14 ± 2 of erdafitinib administration , and more specifically on day 14.

[0095] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0096] The present invention relates to erdafitinib for use in treating cancer in a cancer patient, the specific The above-mentioned patients were treated with erdafitinib at a continuous dose of 8 mg once daily. Patients had serum phosphate levels below 5.5 mg / dL and showed no early developmental toxicity. If not, erdafitinib will be administered continuously daily, specifically once daily, in an amount of 9 mg. In one embodiment, the present invention relates to erdafitinib for use in treating cancer in a cancer patient. In the study, serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment. Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. can be.

[0097] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0098] The present invention relates to erdafitinib for use in treating cancer in a cancer patient, the specific The above-mentioned patients were treated with erdafitinib at a continuous dose of 8 mg once daily. If the patient's serum phosphate concentration is less than 7 mg / dL or / dL, and no early developmental toxicity. Unless otherwise indicated, erdafitinib is administered in an amount of 9 mg daily, specifically once daily, continuously. The present invention relates to erdafitinib for use in treating cancer in a cancer patient, the erdafitinib being administered intravenously to a patient with cancer. The phosphate concentration is in the range of 7 mg / dL to 9 mg / dL, inclusive, and If no early developmental toxicity is observed, combination therapy with phosphate binders such as sevelamer may be appropriate. In one embodiment, combination therapy with a phosphate binder, such as sevelamer, may be initiated. In one embodiment, serum phosphate concentrations are measured at the first day of erdafitinib treatment. More specifically, on treatment days between cycles, specifically on days 14 ± 2 of erdafitinib administration. Physical measurements are taken on the 14th day.

[0099] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0100] In one embodiment of the present invention, serum phosphate concentration (the amount of erdafitinib is increased to 8 mg / kg daily) g daily to 9 mg daily) Concentrations and serum phosphate are assessed once steady-state levels have been reached.

[0101] In one embodiment of the invention, the amount of erdafitinib is increased from 8 mg daily to 9 mg daily. Serum phosphate concentrations were assessed at the first stage of erdafitinib treatment to determine whether the On treatment days during one cycle, specifically on approximately day 14 ± 2 of erdafitinib treatment Specifically, on day 14 of erdafitinib treatment (cycle 1 of erdafitinib treatment) In one embodiment, the cycle is 21 days. The cycle is 28 days.

[0102] The daily amounts of erdafitinib referred to herein may be administered in one pharmaceutical composition, The pharmaceutical agent referred to herein may be administered in the form of more than one pharmaceutical composition. The pharmaceutical composition may also include two or more pharmaceutical compositions. Rudafitinib is available in two formulations, each containing 4 mg of erdafitinib. It can be administered as a tablet. In one embodiment, the 9 mg dose of erdafitinib is administered in three It can be administered as a formulation of erdafitinib, specifically as three tablets containing 3 mg of erdafitinib each. do.

[0103] The present invention provides a method of treating cancer, comprising: a) 8 mg of erdafitinib daily to subjects in need thereof, specifically cancer patients , specifically, once daily and continuously; b) Subjects' serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment. , specifically measured on day 14 ± 2 of erdafitinib administration, more specifically measured on day 14 To do; c-1) If serum phosphate concentration is less than 5.5 mg / dL, erdafitinib should be administered at a dose of 9 mg administered continuously daily, specifically once a day; c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If your blood sugar level is below 8 mg, erdafitinib should be administered daily, specifically once daily. , administered successively further; c-3) If serum phosphate concentration is 7 mg / dL or higher, erdafitinib treatment is The treatment was temporarily discontinued until serum phosphate levels were below 5.5 mg / dL, and then Eldaf Treatment with rifametinib should be resumed daily, specifically at a continuous dose of 8 mg once daily. The present invention relates to a method comprising the steps of:

[0104] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0105] The present invention provides a method of treating cancer, comprising: a) 8 mg of erdafitinib daily to subjects in need thereof, specifically cancer patients , specifically, once daily and continuously; b) Subjects' serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment. , specifically measured on day 14 ± 2 of erdafitinib administration, more specifically measured on day 14 To do; c-1) Serum phosphate concentration is less than 7 mg / dL, or In the range of 7 mg / dL to 9 mg / dL, including mg / dL, erdafitin The drug is administered continuously daily, specifically once daily, in an amount of 9 mg; and serum phosphorus For example, if the acid salt concentration is in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL, Concomitant therapy with a phosphate binder, such as sevelamer, is optionally initiated; c-2) If serum phosphate concentration is >9 mg / dL, erdafitinib treatment should be continued until serum Temporarily discontinued until phosphate levels were < 7 mg / dL, then erdafitini Treatment should be resumed daily, specifically at 8 mg continuously once daily. The present invention relates to a method comprising the steps of:

[0106] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0107] The present invention provides a method of treating cancer, comprising: a) 8 mg of erdafitinib daily to subjects in need thereof, specifically cancer patients , specifically, once daily and continuously; b) Subjects' serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment. , specifically measured on day 14 ± 2 of erdafitinib administration, more specifically measured on day 14 To do; c-1) Serum phosphate concentration is less than 5.5 mg / dL and no early developmental toxicity is observed. If not, erdafitinib should be administered in a dose of 9 mg daily, specifically once daily, continuously. administered; c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If the clinical response rate is within the range of 8m and no early developmental toxicity is demonstrated, erdafitinib should be administered at g of the drug is administered continuously daily, specifically once a day; c-3) Serum phosphate concentration is 7 mg / dL or more and no early developmental toxicity is observed. If not, erdafitinib treatment should be continued until serum phosphate levels are <5.5 mg / dL. The erdafitinib treatment is then temporarily discontinued and then resumed daily, specifically once daily, without interruption. The drug should be resumed at a dose of 8 mg. The present invention relates to a method comprising the steps of:

[0108] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0109] The present invention provides a method of treating cancer, comprising: a) 8 mg of erdafitinib daily to subjects in need thereof, specifically cancer patients , specifically, once daily and continuously; b) Subjects' serum phosphate concentrations were measured on the treatment day during the first cycle of erdafitinib treatment. , specifically measured on day 14 ± 2 of erdafitinib administration, more specifically measured on day 14 To do; c-1) Serum phosphate concentration is less than 7 mg / dL and no early developmental toxicity is observed. or serum phosphate concentration is 7 mg / dL to 9 mg / dL (including 7 mg / dL) If the dose is in the range of 10 mg / kg and no early developmental toxicity is demonstrated, erdafitinib should be administered at a dose of 9 mg / kg. and the serum phosphate concentration is maintained at 7 m g / dL, in the range of 7 mg / dL to 9 mg / dL or less, e.g., sevelamer Combination therapy with phosphate binders such as sirolimus or sirolimus is optionally initiated; c-2) Serum phosphate concentration is greater than 9 mg / dL and no early developmental toxicity is observed If so, erdafitinib treatment should be discontinued until serum phosphate levels are reduced to <7 mg / dL. Erdafitinib treatment was then discontinued daily, specifically once daily, for 8 consecutive days. mg. The present invention relates to a method comprising the steps of:

[0110] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0111] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. There was, a) the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically once a day for successive administrations of b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) If serum phosphate concentration is less than 5.5 mg / dL, daily, specifically once a day The amount of erdafitinib in the drug product for continuous administration was increased to 9 mg at c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If the range is less than 8 mg, the patient should be placed on continuous treatment with 8 mg daily, specifically once daily. Stop; c-3) If serum phosphate concentration is 7 mg / dL or higher, erdafitinib treatment is The treatment was temporarily discontinued until serum phosphate levels were below 5.5 mg / dL, and then Eldaf Eldifference in time, eldifference in time, eldifference in time, eldifference in time, Regarding the use of tinib.

[0112] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0113] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. There was, a) the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically once a day for successive administrations of b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 7 mg / dL, or If your blood sugar level is between 7 mg / dL and 9 mg / dL, including mg / dL, The amount of erdafitinib in the drug product for continuous administration was increased to 9 mg once daily. and serum phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL If the range is within the range, combination therapy with a phosphate binder, such as sevelamer, is optionally initiated. Re; c-2) If serum phosphate concentration is >9 mg / dL, erdafitinib treatment should be continued until serum Temporarily discontinued until phosphate levels were < 7 mg / dL, then erdafitini Erdafitinib treatment is resumed daily, specifically at 8 mg once daily. Regarding the use of.

[0114] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0115] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. There was, a) the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically once a day for successive administrations of b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 5.5 mg / dL and no early developmental toxicity is observed. If not possible, erdaphytin in medicines for continuous administration daily, specifically once a day Nib quantity increased to 9mg; c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If the dose is within the range of 0.01 mg / dose and no early developmental toxicity is observed, patients should be treated with 8 mg / dose Physically, treatment should be limited to one continuous session per day; c-3) Serum phosphate concentration is 7 mg / dL or more and no early developmental toxicity is observed. If not, erdafitinib treatment should be continued until serum phosphate levels are <5.5 mg / dL. The erdafitinib treatment is then temporarily discontinued and resumed daily, specifically once daily, Regarding the use of erdafitinib, which was resumed at a dose of 8 mg.

[0116] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0117] The present invention relates to the use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. There was, a) the drug product contains erdafitinib in an amount of 8 mg, and the drug product is administered daily, specifically once a day for successive administrations of b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 7 mg / dL and no early developmental toxicity is observed. or serum phosphate concentration is 7 mg / dL to 9 mg / dL (including 7 mg / dL) If the range is within the range of 100 mg / kg / day and no early developmental toxicity is observed, then daily, specifically once a day, The amount of erdafitinib in the drug product for continuous administration was increased to 9 mg; and serum Phosphate concentration is between 7 mg / dL and 9 mg / dL, including 7 mg / dL , combination therapy with a phosphate binder, such as sevelamer, is optionally initiated; c-2) Serum phosphate concentration is greater than 9 mg / dL and no early developmental toxicity is observed If so, erdafitinib treatment should be discontinued until serum phosphate levels are reduced to <7 mg / dL. Erdafitinib treatment was then discontinued daily, specifically once daily, for 8 consecutive days. Regarding the use of erdafitinib, which will be resumed at 2 mg.

[0118] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0119] The present invention relates to a) erdafitinib is administered continuously daily, specifically once daily, in an amount of 8 mg; b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) If serum phosphate concentration is less than 5.5 mg / dL, erdafitinib is administered for 9 mg administered continuously daily, specifically once a day; c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If your blood sugar level is below 8 mg, erdafitinib should be administered daily, specifically once daily. , administered successively further; c-3) If serum phosphate concentration is 7 mg / dL or higher, erdafitinib treatment is The treatment was temporarily discontinued until serum phosphate levels were below 5.5 mg / dL, and then Eldaf In a cancer patient, rituximab treatment is resumed daily, specifically at 8 mg once daily. The present invention relates to erdafitinib for use in the treatment of

[0120] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0121] The present invention relates to a) erdafitinib is administered continuously daily, specifically once daily, in an amount of 8 mg; b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 7 mg / dL, or In the range of 7 mg / dL to 9 mg / dL, including mg / dL, erdafitin 9 mg of riboflavin is administered continuously daily, specifically once daily; and For example, if the acid salt concentration is in the range of 7 mg / dL to 9 mg / dL, including 7 mg / dL, Concomitant therapy with a phosphate binder, such as sevelamer, is optionally initiated; c-2) If serum phosphate concentration is >9 mg / dL, erdafitinib treatment should be continued until serum Temporarily discontinued until phosphate levels were < 7 mg / dL, then erdafitini Treatment of cancer in a cancer patient in which steroid therapy is resumed daily, specifically at 8 mg once daily. The present invention relates to erdafitinib for use in

[0122] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0123] The present invention relates to a) erdafitinib is administered continuously daily, specifically once daily, in an amount of 8 mg; b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 5.5 mg / dL and no early developmental toxicity is observed. If this is not possible, erdafitinib should be administered at a dose of 9 mg daily, specifically once daily continuously. administered; c-2) Serum phosphate concentration is between 5.5 mg / dL and 7 mg / dL, including 5.5 mg / dL If the clinical response rate is within the range of 8m and no early developmental toxicity is demonstrated, erdafitinib should be administered at g of the drug is administered continuously daily, specifically once a day; c-3) Serum phosphate concentration is 7 mg / dL or more and no early developmental toxicity is observed. If not, erdafitinib treatment should be continued until serum phosphate levels are <5.5 mg / dL. The erdafitinib treatment is then temporarily discontinued and resumed daily, specifically once daily, Erdafitinib for use in the treatment of cancer in cancer patients to be resumed at a target dose of 8 mg .

[0124] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 3. can be managed according to

[0125] The present invention relates to a) erdafitinib is administered continuously daily, specifically once daily, in an amount of 8 mg; b) the patient's serum phosphate concentration on the treatment day during the first cycle of erdafitinib treatment: Specifically, it was measured on day 14 ± 2 of erdafitinib administration, more specifically on day 14. Re; c-1) Serum phosphate concentration is less than 7 mg / dL and no early developmental toxicity is observed. or serum phosphate concentration is 7 mg / dL to 9 mg / dL (including 7 mg / dL) If the dose is in the range of 10 mg / kg and no early developmental toxicity is demonstrated, erdafitinib should be administered at a dose of 9 mg / kg. and the serum phosphate concentration is maintained at 7 m g / dL, in the range of 7 mg / dL to 9 mg / dL or less, e.g., sevelamer Combination therapy with phosphate binders such as sirolimus or sirolimus is optionally initiated; c-2) Serum phosphate concentration is greater than 9 mg / dL and no early developmental toxicity is observed If so, erdafitinib treatment should be discontinued until serum phosphate levels are reduced to <7 mg / dL. Erdafitinib treatment was then discontinued daily, specifically once daily, for 8 consecutive days. The study is being re-launched at 2 mg for erdafitinib for use in the treatment of cancer in cancer patients.

[0126] In one embodiment, the serum phosphate concentration during further erdafitinib administration is as shown in Table 4. can be managed according to

[0127] The methods of treatment and use described herein rely on phosphate concentration as a pharmacodynamic marker. It should be understood that these may be modified or discontinued based on toxicity. In embodiments, treatment or use is altered or discontinued as described in Table 1.

[0128] [Table 1]

[0129] Erdafitinib is discontinued, specifically for 1 week consecutively due to drug-related toxicity. If discontinued, it should be discontinued at the same dose level or after the first reduction, after recovery from toxicity. In one embodiment, the erdafitinib dose reduction level can be reintroduced at a reduced dose. The dosage regimen is as described in Table 2. The second dose reduction was performed to reduce the incidence of a second occurrence of drug-related toxicity. Later, this can be carried out specifically as described in Table 2.

[0130] [Table 2]

[0131] Treatment with erdafitinib or its administration should be discontinued when, for example, Tolerable levels of non-hematological toxicity (Grade 1 or less or return to baseline) If the patient must be withheld for longer than 28 days due to a drug-related adverse event that does not resolve within 28 days It is up to the physician's discretion to decide whether to continue treatment if the patient is benefiting from it. To demonstrate that continued treatment with erdafitinib is in the best interest of the patient, It should be understood that erdafitinib can be dose-reduced and that this dose-reducing If the adverse event that caused the reduction has completely resolved, the dose is reduced to ensure that the patient is benefiting from the treatment. If the patient is unable to tolerate the erdafitinib dose, the dose may be re-escalated to the next higher level, and the physician may It can show what is most beneficial for the patient.

[0132] Patients with any grade of toxicity (grades 1–4) should receive symptomatic treatment, if applicable. You have to understand that you have to give.

[0133] In one embodiment, treatment with erdafitinib is discontinued as described herein. Assessment of serum phosphate if serum phosphate concentrations are monitored until they return to the levels indicated. Evaluations are performed at least weekly.

[0134] In one embodiment, treatment with erdafitinib is inducible in the treatment of hyperphosphatemia as described herein. If the suspension is for a period of about seven days, specifically seven days.

[0135] Serum phosphate concentrations, specifically on the treatment day during the first cycle of erdafitinib treatment , specifically measured on day 14 ± 2 of erdafitinib administration, more specifically measured on day 14 To determine whether to escalate the starting dose of erdafitinib to 8 mg Phosphate concentrations, when measured as a marker of toxicity, should be further monitored during erdafitinib treatment. It should be understood that the clinical management of serum phosphate concentrations may be considered. is performed as shown in Table 3.

[0136] [Table 3]

[0137] In one embodiment, clinical management of serum phosphate concentrations is performed as depicted in Table 4. do.

[0138] [Table 4]

[0139] To manage elevated phosphates, restriction of daily phosphate intake may be required. It should be understood.

[0140] To manage elevated phosphate, patients should be concurrently treated with, for example, sevelamer phosphate (p It should be understood that patients may need to take phosphate binders such as phosphate binders. be.

[0141] The tumor response assessments reported herein are Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 . was carried out in accordance with.

[0142] The present invention relates to erdafitinib formulations and dosing regimens described herein. It also relates to packaging containing such information, for example patient leaflets.

[0143] In one embodiment, the cancer referred to herein is a cancer mediated by FGFR kinases. It's cancer.

[0144] In one embodiment, the cancer is bladder cancer.

[0145] In one embodiment, the cancer is hepatocellular carcinoma.

[0146] In one embodiment, the cancer is squamous cell carcinoma.

[0147] In one embodiment, the cancer is squamous NSCLC (non-small cell lung cancer), specifically, selected Specifically, squamous cell NSCLC (non-small cell lung cancer) with FGFR gene alterations The study aimed to evaluate the efficacy and safety of FGFR gene alterations in patients with squamous NSCLC (non-small cell lung cancer) with relapse after standard treatment. The treatment of cancer in patients with pulmonary arterial disease (pulmonary small cell carcinoma).

[0148] In one embodiment, the cancer is hepatocellular carcinoma with FGF19 amplification or overexpression.

[0149] In one embodiment, the cancer is cholangiocarcinoma, particularly advanced or metastatic cholangiocarcinoma.

[0150] In one embodiment, the cancer is urothelial carcinoma.

[0151] In one embodiment, the cancer is metastatic or surgically unresectable urothelial carcinoma.

[0152] In one embodiment, the cancer is an aggressive urothelial cancer with a selected FGFR genetic alteration. Cancer, particularly selected FGFR1, that has progressed on or after one previous treatment. The treatment of cancer in patients with advanced urothelial carcinoma who have genetic alterations.

[0153] In one embodiment, the cancer is lung cancer, specifically non-small cell lung cancer.

[0154] In one embodiment, the cancer is adenoid cystic carcinoma, mucoepidermoid carcinoma, follicular thyroid carcinoma, breast cancer, Ewing's Sarcoma, small round cell bone tumors ), synovial sarcoma, glioblastoma multiforme, pilocytic astrocytoma, lung cancer, clear cell renal cell carcinoma, bladder cancer, prostate cancer, ovarian cancer, and colon cancer.

[0155] In one embodiment, the cancer is multiple myeloma, specifically t(4;14) translocation positive multiple myeloma. It is myeloma.

[0156] In one embodiment, the cancer is non-muscle invasive bladder cancer, specifically cancer characterized by FGFR genomic alterations (e.g. For example, non-muscle invasive bladder cancer with multiple myeloma (e.g., translocations, fusions, and / or mutations).

[0157] In one embodiment, the cancer is esophageal cancer or head and neck cancer.

[0158] In one embodiment, the cancer is gastric cancer.

[0159] In one embodiment, the cancers referred to herein are characterized by FGFR genomic alterations (e.g., translocations , fusions, and / or mutations), particularly in cancers sensitive to erdafitinib Cancers with genome alterations (e.g., translocations, fusions, and / or mutations), such as FGFR genome alterations Bladder cancer with alterations (e.g., translocations, fusions, and / or mutations) or FGFR genomic alterations urothelial carcinoma with FGFR genomic alterations (e.g., translocations, fusions, and / or mutations) Metastatic or surgically unresectable urinary tract disease (e.g., translocations, fusions, and / or mutations) epithelial carcinoma or bile duct with FGFR genomic alterations (e.g., translocations, fusions, and / or mutations) Cancer or progressive young adulthood with FGFR genomic alterations (e.g., translocations, fusions, and / or mutations). or metastatic bile duct cancer.

[0160] In one embodiment, the cancer referred to herein is characterized by the following fusion FGFR3:TACC3: v1;FGFR3:TACC3 v3;FGFR3:TACC3 intron;FGFR 3:BAIAP2L1;FGFR2:AFF3;FGFR2:BICC1;FGFR2: Alterations selected from CASP7;FGFR2:CCDC6, and FGFR2:OFD1 It is a cancer that has

[0161] In one embodiment, the cancer referred to herein is a cancer characterized by FGFR3-TACC3 fusion or translocation. Cancers with FGFR3-TACC3 translocations, e.g., bladder cancers with FGFR3-TACC3 translocations, or Urothelial carcinoma with TACC3 translocation or metastatic young carcinoma with FGFR3-TACC3 translocation or surgically unresectable urothelial carcinoma.

[0162] In one embodiment, the cancer referred to herein is characterized by the following FGFR3 gene mutations: FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, FGFR 3 Y373C.

[0163] In one embodiment, the cancer referred to herein is characterized by the following FGFR3 gene mutations: FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, FGFR 3 Bladder cancer, urothelial carcinoma, or metastatic or Surgically unresectable urothelial carcinoma.

[0164] In one embodiment, a subject in need of treatment for a cancer referred to herein, in particular The use for treating cancer in a cancer patient or the method for treating cancer may be such that the tumor is a selected FGFR genomic DNA. Patients with genomic changes and who have had at least one prior line of systemic chemotherapy during or after chemotherapy or failure of neoadjuvant or adjuvant chemotherapy within 12 months or chemotherapy-naïve but cisplatin-ineligible, metastatic or surgical The present invention relates to use for or treatment of patients with partially unresectable urothelial carcinoma.

[0165] In one embodiment, a subject in need of treatment for a cancer referred to herein, in particular The use for treating cancer in a cancer patient or the method for treating cancer may include administering luminal clusters (lumin for use in patients with (i) al cluster I subtype urothelial carcinoma or for the treatment of patients It is treatment.

[0166] In one embodiment, erdafitinib is administered as a pharma- ceutically acceptable salt.

[0167] In a preferred embodiment, erdafitinib (base) is administered.

[0168] In one embodiment, erdafitinib is administered in an amount equivalent to 8 mg base equivalent, or 9 mg salt equivalent. It is administered as a pharma- ceutically acceptable salt in an amount corresponding to the base equivalent.

[0169] The salts can be prepared, for example, by reacting erdafitinib with a suitable acid in a suitable solvent. It can be prepared.

[0170] Acid addition salts can be formed with both inorganic and organic acids. Examples of acid addition salts include acetic acid. Acid, hydrochloric acid, hydroiodic acid, phosphoric acid, nitric acid, sulfuric acid, citric acid, lactic acid, succinic acid, maleic acid acid, malic acid, isethionic acid, fumaric acid, benzenesulfonic acid, toluenesulfonic acid , methanesulfonic acid (mesylate), ethanesulfonic acid, naphthalenesulfonic acid, valeric acid , acetic acid, propionic acid, butanoic acid, malonic acid, glucuronic acid, and lactobionic acid. Another group of acid addition salts includes salts formed with acids selected from the group consisting of acetic acid, adipic acid, and acetic acid. 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 Among the salts formed from the acids sebacic acid, stearic acid, succinic acid, and tartaric acid.

[0171] In one embodiment, erdafitinib is administered in the form of a solvate. The term "solvate" means a physical association of erdafitinib with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain cases, solvates exist, e.g., when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. If solvated, it may be possible to isolate it. Non-limiting examples of solvents that may form solvates include , water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, or Ethanolamine, etc.

[0172] Solvates are well known in pharmaceutical chemistry. They occur during the process of preparation of a substance (e.g. With respect to these purifications, the preservation of the material (e.g., its stability) and the ease with which the material can be handled are important considerations. can be important for the synthesis of cyclic amines and are often formed as part of the isolation or purification steps of chemical synthesis. Those skilled in the art will recognize that standard and long-established techniques are used to prepare a given compound. It can be determined whether hydrates or other solvates were formed due to the isolation or purification conditions used. 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 (SS- NMR, also known as magic angle spinning NMR or MAS-NMR). The techniques used are NMR, IR, HPLC, and MS, as well as standard analytical techniques used by skilled chemists. Alternatively, one of skill in the art can easily determine the amount of solvent required for a particular solvate. Crystallization conditions can be used to deliberately form solvates, which can then be reacted with the standard methods described above. The formation of solvates can be confirmed using the Also includes inclusion complexes or clathrates with compounds such as rhodextrin, or complexes with metals. Included.

[0173] In one embodiment, the treatment cycle herein is a 28 day cycle.

[0174] In one embodiment, the patients herein, particularly cancer patients, or patients receiving erdafitinib therapy, The subject in need of treatment is a human.

[0175] As used herein in connection with numerical values, the term "about" has its ordinary meaning in the context of the numerical value. Where necessary, the word "about" shall mean a numerical value ±10%, or ±5%, or ± 2%, or ±1%.

[0176] All documents cited herein are incorporated by reference in their entirety. EXAMPLES

[0177] Ongoing Phase 2, multicenter, open-label study (NCT02365597) A phase 2, multicenter, open-label study is being conducted to evaluate select FGFR gene alterations (FGFR translocations or Eldafi in subjects with metastatic or surgically unresectable urothelial carcinoma with This is being conducted to evaluate the efficacy and safety of tinib.

[0178] The study will include a screening phase (molecular screening and This includes the study screening (within 30 days of first administration), the treatment period, and the post-treatment follow-up period. The treatment period includes the period from the first dose to the end-of-treatment visit. Death, withdrawal of consent, loss to follow-up, or termination of the study, whichever occurs first will be extended until

[0179] The study treatment will be administered in 28-day cycles. Prior to interim analysis 1, two treatment regimens were Patients were randomized to receive one of two regimens until a regimen was selected for further study: Patients were randomized 1:1 to receive either Regimen 1 (10 mg once daily) or Regimen 2 (10 mg once daily) for 28 days. Intermittent (7 days / 7 days); Regimen 2 (6 mg once daily continuously). After interim analysis 1, Pharmacokinetic and pharmacodynamic models relating rudafitinib dosing regimens to serum phosphate concentrations Based on the results of the ring, the protocol was amended to a starting dose of 8 mg / day continuous dosing. (Regimen 3) and on day 14, the target serum phosphate concentration was not reached at that time (serum Patients with phosphate levels <5.5 mg / dL) and no treatment-related adverse events were observed. In patients who did not receive the treatment, the dose was titrated up to 9 mg / day. Dose reduction based on E)) was anticipated in the protocol.

[0180] Please refer to Figure 1 for the Phase 2 study scheme.

[0181] patient Patients enrolled met the Response Evaluation Criteria Patients with measurable urothelial carcinoma according to the US in Solid Tumors version 1.1 He was an adult.

[0182] Patients will receive a custom assay from formalin-fixed, paraffin-embedded tumor samples. At least one FGFR2 / FGFR3 mutation was detected according to central laboratory testing of RNA from It was required to have a mutation or fusion.

[0183] Patients were randomly assigned to receive 12 or more lines of chemotherapy during or after at least one prior line of systemic chemotherapy. had progressed on neoadjuvant or adjuvant chemotherapy for less than a month.

[0184] Chemotherapy-naïve patients who were cisplatin-ineligible based on protocol criteria were accepted. The inappropriateness of cisplatin was as follows: 1) 24-hour urine measurement of 60 mL / min / 1.73 m 2 2) Glomerular filtration rate less than 0.05%; 2) Cockcroft-Gault calculation; or 3) Grade 2 or greater Common Terminology Criteria for Peripheral Neuropathy Adverse Events [CTCAE] Version 4.0 (National Cancer Institute.CTCAE v4.0.NCI,NIH,DHHS .May 29,2009.NIH publication#09-7473:200 9.) was based on renal dysfunction, defined as

[0185] Eastern Cooperative Oncology Group (ECOG) ) Performance status 0-2 was requested.

[0186] There was no limit to the number of prior lines of therapy.

[0187] Prior immunotherapy (e.g., treatment with PD-L1 / PD-1 inhibitors) was accepted.

[0188] Patients must have adequate bone marrow, liver, and renal (creatinine clearance ≥ 40 mL / min) function. It was required that the company have the following:

[0189] Phosphate levels that are persistently above the upper limit despite medical management, control Patients with adverse cardiovascular disease, brain metastases, known hepatitis B or C, or known HIV were excluded.

[0190] Endpoints The primary endpoint of this ongoing study is the efficacy and safety of the selected regimen (regimen 3). ) and the objective response rate. Secondary endpoints were progression-free survival (P FS), duration of response (DoR), overall survival, safety, predictive biomarker evaluation, and drug There is a dynamic.

[0191] evaluation Patients will be randomly assigned to receive a 24-hour period within 30 days of screening, once every 6 weeks for the first 3 months, and once every 9 months for the next 24 months. Radiographic imaging was performed once every 12 weeks, then once every 4 to 6 months until disease progression. was used to evaluate efficacy.

[0192] Tumor response was assessed according to RECIST version 1.1 (Eisenhauer EA et al. l., Eur J Cancer, 2009, 45(2), 228-247) Assessed by the investigator.

[0193] Safety was assessed by the investigator through medical review of AE reports and vital sign measurements. Results of clinical trials, physical examinations, laboratory tests, ECOG performance status, and other safety assessments. The patients were serially evaluated based on the results.

[0194] result Baseline characteristics and efficacy data were collected from May 7, 2015 to June 10, 2017. The patients were enrolled and evaluable for response according to RECIST 1.1. The results are presented for 170 patients who were considered to be able to receive the treatment (Table 5).

[0195] Safety data were collected from safety analyses defined as patients who received at least one dose of study treatment. Regarding the elephant population (N=207, enrolled between May 7, 2015 and December 5, 2017), As of December 5, 2017, the median treatment duration was 4.2 months, and patients received a median The patient had received five cycles of erdafitinib.

[0196] During the screening phase, 21% of patients had FGFR mutations or fusions that met the inclusion criteria. Had.

[0197] Across regimens, 89% had received at least one prior line of systemic chemotherapy It was progressing.

[0198] [Table 5]

[0199] Across all treatment regimens, the confirmed objective response rate was 35% (95% CI, 28% to 43%). The highest rate was achieved with continuous erdafitinib at 8 mg / day in regimen 3. The confirmed disease control rate was 76% among all patients. The majority of patients treated with erdafitinib at 8 mg / day had tumor had a reduction in volume (44 / 59 [75%] had a reduction in the sum of target lesion diameters; Figure 2) .

[0200] The median progression-free survival was 5.1 months with continuous 8 mg / day therapy in regimen 3. was longest among patients treated with erdafitinib (Table 6).

[0201] The median duration of response in the continuous erdafitinib 8 mg / day group (regimen 3) was 5 .4 months, with many responses ongoing (Table 6).

[0202] [Table 6]

[0203] Time to response In the subset of 59 patients on Regimen 3, the median time to response was 1.41 months, ranging from 1.1 to 5.5 months.

[0204] Across all treatment regimens, 94% (n=195) of patients reported TRAEs; most of these All were grade 1 or 2 (Table 7).

[0205] Thirty-three percent (n=69) of patients reported grade 3 TRAEs, and 0.5% (n=1) Patients reported no grade 4 TRAEs and no treatment-related deaths.

[0206] AEs were manageable.

[0207] Recommendations for prevention of major AEs associated with erdafitinib treatment: A low-phosphate diet was recommended for all patients to reduce the risk of hyperphosphatemia (10 mg / day dietary phosphate intake of 600-800 mg per day). Application of an alcohol-free, emollient, moisturizing cream to reduce the risk of skin reactions and avoiding unnecessary exposure to sunlight, soaps, perfumed products, and hot baths. It was recommended that: To reduce the risk of nail reactions, it is recommended that patients keep their hands and feet clean and their nails trimmed. It was recommended.

[0208] management Hyperphosphatemia (>5.5 mg / dL) should be managed with phosphate binders if medically justified. It was done. Dry skin can be treated with additional topical creams such as ammonium lactate, salicylic acid, or zinc oxide creams. The condition was managed with topical ointment. Nail effects were managed with topical nail strengtheners; in severe cases, antibiotics or silver nitrate were applied. It was done.

[0209] TRAEs associated with the FGFR inhibitor class were typically grade 1 or 2 Across all treatment regimens, two patients reported retinopathy (Grade 2 [n=1] and Grade 4 [n=2]). 3[n=1]).

[0210] Across all dosing regimens, 22 patients (11%) discontinued as a result of TRAEs. The most common TRAEs leading to discontinuation were asthenia, xerostomia, and palmar-plantar erythema. It was a deficiency syndrome.

[0211] [Table 7]

Claims

1. A method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, a serum phosphate Salt concentration is in the range of 5.5 mg / dL to less than 7 mg / dL, including 5.5 mg / dL or in the range of 5.5 mg / dL to 9 mg / dL, inclusive. The method comprises administering an amount of erdafitinib to a patient in need thereof.

2. the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL The method of claim 1 , wherein the range is less than 100 μm.

3. Serum phosphate concentration between 5.5 mg / dL and less than 7 mg / dL, including 5.5 mg / dL or in the range of 5.5 mg / dL to 9 mg / dL, inclusive. Use of erdafitinib in the manufacture of a medicament for the treatment of cancer in an amount in the range For.

4. the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL The use according to claim 3, wherein the range is less than 100 mg / kg.

5. Erdafitinib was administered to patients with a serum phosphate concentration of 5.5 mg / dL or higher. to less than 7 mg / dL or between 5.5 mg / dL and and 5 mg / dL or less of erythrocytes for use in the treatment of cancer. Dafitinib.

6. the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL Erdafitinib for use according to claim 4, wherein the range is less than 100 mg / kg.

7. A method of treating cancer, comprising administering to a subject in need thereof, particularly a cancer patient, 8 mg of endothelial cell carcinoma. A method comprising administering rudafitinib continuously every day, specifically once a day.

8. Use of erdafitinib for the manufacture of a medicament for the treatment of cancer, said medicament comprising and the pharmaceutical product is administered daily, specifically once a day, in a continuous manner. The use of erdafitinib for continuous administration.

9. Erdafitinib is administered in an amount of 8 mg daily, specifically once daily continuously. Erdafitinib for use in the treatment of

10. The cancer is urothelial carcinoma, bladder cancer, hepatocellular carcinoma, squamous cell carcinoma, or lung cancer.

10. The method or use according to any one of claims 9 to 9.

11. 11. The method of claim 10, wherein the cancer is metastatic or surgically unresectable urothelial carcinoma. is used.

12. 11. The method or use of claim 10, wherein the cancer is advanced or metastatic cholangiocarcinoma.

13. 1. A method of treating cancer, comprising: a) subjects in need thereof, specifically cancer patients, receive 8 mg of erdafitinib daily. , specifically once daily on a continuous basis; b) monitoring the subject's serum phosphate concentration during the first cycle of erdafitinib treatment On the day of administration of erdafitinib, specifically on the 14th day ± 2 days, more specifically on the 14th day Measuring c-1) if the serum phosphate concentration is less than 5.5 mg / dL, erdafitinib , administered continuously daily, specifically once a day, in an amount of 9 mg; c-2) the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL In the range of less than 10 ... one further dose administered consecutively; c-3) When the serum phosphate concentration is 7 mg / dL or more, the erdafitinib treatment is The treatment is temporarily discontinued until serum phosphate levels are below 5.5 mg / dL, and then Erdafitinib treatment is resumed daily, specifically at 8 mg continuously once daily. The method includes:

14. Use of erdafitinib for the manufacture of a medicament for the treatment of cancer in a cancer patient. a) the pharmaceutical product comprises erdafitinib in an amount of 8 mg, and the pharmaceutical product is administered daily, specifically is for continuous administration once daily; b) the patient's serum phosphate concentration is determined on treatment day 1 during the first cycle of erdafitinib treatment Specifically, the measurement was performed on day 14 ± 2 of erdafitinib administration, and more specifically on day 14. It is determined; c-1) If the serum phosphate concentration is less than 5.5 mg / dL, then daily, specifically once a day The amount of erdafitinib in the drug product for continuous administration once daily is increased to 9 mg. ； c-2) the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL If the patient is in the range of less than 800 mg / day, specifically once daily, Remain in treatment; c-3) When the serum phosphate concentration is 7 mg / dL or more, the erdafitinib treatment is The treatment is temporarily discontinued until serum phosphate levels are below 5.5 mg / dL, and then Erdafitinib treatment is resumed daily, specifically at 8 mg once daily. For.

15. Erdafitinib for use in treating cancer in a cancer patient. a) erdafitinib is administered continuously daily, specifically once daily, in an amount of 8 mg; b) the patient's serum phosphate concentration is determined on treatment day 1 during the first cycle of erdafitinib treatment Specifically, the measurement was performed on day 14 ± 2 of erdafitinib administration, and more specifically on day 14. It is determined; c-1) if the serum phosphate concentration is less than 5.5 mg / dL, erdafitinib , administered continuously daily, specifically once a day, in an amount of 9 mg; c-2) the serum phosphate concentration is 5.5 mg / dL to 7 mg / dL, including 5.5 mg / dL In the range of less than 10 ... one further dose administered consecutively; c-3) When the serum phosphate concentration is 7 mg / dL or more, the erdafitinib treatment is The treatment is temporarily discontinued until serum phosphate levels are below 5.5 mg / dL, and then Erdafitinib treatment is resumed daily, specifically at 8 mg once daily. Rudafitinib.

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