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Fgfr1 extracellular domain combination therapies

a combination therapy and extracellular domain technology, applied in the field of fgfr1 extracellular domain combination therapy, can solve the problems of additive, synergistic, or antagonistic effects on the efficacy of each of the anti-cancer therapy, and achieve the effect of inhibiting tumor cell growth

Inactive Publication Date: 2015-07-23
FIVE PRIME THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method of treating cancer by combining a soluble form of FGFR1 (FGFR1 ECD) with other therapeutic agents such as docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-FU, leucovorin, pemetrexed, etoposide, topotecan, a vascular epithelial growth factor (VEGF) antagonist, a VEGF trap, an anti-VEGF antibody, and bevacizumab. The combination of these agents can have synergistic or additive effects on inhibiting tumor growth in mouse xenograft models. The patent also describes the use of FGFR1 ECD in combination with other therapeutic agents such as pemetrexed, etoposide, topotecan, a vascular epithelial growth factor (VEGF) antagonist, a VEGF trap, an anti-VEGF antibody, and bevacizumab. The patent provides various methods for using the combination of these agents to treat cancer.

Problems solved by technology

Combining an anti-cancer therapeutic molecule, such as a soluble form of FGFR1, with another anti-cancer therapeutic molecule, can result in antagonistic, additive, or synergistic effects on the efficacy of each of the anti-cancer therapeutics.

Method used

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  • Fgfr1 extracellular domain combination therapies
  • Fgfr1 extracellular domain combination therapies
  • Fgfr1 extracellular domain combination therapies

Examples

Experimental program
Comparison scheme
Effect test

example 1

Administration of FGFR1-ECD.339-Fc and Docetaxel in the H1703 Non-Small Cell Lung Cancer (NSCLC) Xenograft Model

[0154]Six week old female SCID mice were purchased from Charles River Laboratories (Wilmington, Mass.) and were acclimated for 1 week before the start of the study. Human non-small cell lung cancer (NSCLC) cell line H1703 was used as the tumor model and was purchased from ATCC (Manassas, Va.; Cat. No. CRL-5889). The cells were cultured for three passages in RPMI+10% FBS+1% L-glutamine at 37° C. in a humidified atmosphere with 5% CO2. When the cultured cells reached 85-90% confluence, cells were harvested and resuspended in cold Ca2+ and Mg2+ free phosphate buffered saline (PBS) containing 50% Matrigel at 2.5×107 cells per milliliter. The cells were implanted subcutaneously over the right flank of the mice at 2.5×106 cells / 100 μl / mouse. One day after tumor implantation, mice were randomized according to body weight at 10 mice per group.

[0155]FGFR1-ECD.339-Fc was formulated ...

example 2

Administration of FGFR1-ECD.339-Fc and Pemetrexed in the H520 Non-Small Cell Lung Cancer (NSCLC) Xenograft Model

[0163]Six to eight week old female SCID mice were purchased from Charles River Laboratories (Wilmington, Mass.) and were acclimated for 1 week before the start of the study. Squamous cell lung cancer cell line NCI-H520 was used as the tumor model and was purchased from ATCC (Manassas, Va.; Cat. No. HTB-182). The cells were cultured for three to four passages in RPMI+10% FBS+1% L-glutamine at 37° C. in a humidified atmosphere with 5% CO2. When the cultured cells reached 85-90% confluence, cells were harvested and resuspended in cold Ca2+ and Mg2+ free PBS containing 50% Matrigel at 3.5×107 cells / ml. The cells were implanted subcutaneously over the right flank of the mice at 3.5×106 cells / 100 μl / mouse. One day after tumor implantation, mice were randomized according to body weight at 10 mice per group. Dosing for all groups began one day post tumor implantation.

[0164]FGFR1-E...

example 3

Administration of FGFR1-ECD.339-Fc in Combination with Various Chemotherapeutics in the A549 Non-Small Cell Lung Cancer (NSCLC) Xenograft Model

[0174]Six weeks old female SCID mice were purchased from Charles River Laboratories (Wilmington, Mass.) and were acclimated for 1 week before the start of the study. A549 cells purchased from ATCC (Manassas, Va.; Cat. No. CCL-185) were cultured for three passages in RPMI+10% FBS+1% L-glutamine at 37° C. in a humidified atmosphere with 5% CO2 When the cultured cells reached 85-90% confluence, cells were harvested and resuspended in cold Ca2+ and Mg2+ free phosphate buffered saline (PBS) containing 50% Matrigel at 5×107 cells per milliliter. The cells were implanted subcutaneously over the right flank of the mice at 5×106 cells / 100 μl / mouse. One day after tumor implantation, mice were randomized according to body weight at 10 mice per group.

[0175]The tumor volume and body weight of the mice were monitored twice a week throughout each study. The...

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Abstract

Methods of treating cancer comprising administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and / or an FGFR1 ECD fusion molecule in combination with at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are provided. Dosage packs comprising an FGFR1 ECD and / or an FGFR1 ECD fusion molecule and / or at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are also provided. In some embodiments, a dosage pack comprises instructions for administering FGFR1 ECD and / or FGFR1 ECD fusion molecule with at least one additional therapeutic agent.

Description

RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 13 / 296,168, filed Nov. 14, 2011, which claims priority to U.S. Provisional Application No. 61 / 421,462 filed Dec. 9, 2010, the contents of each of which is incorporated herein by reference in its entirety for any purpose.BACKGROUND AND SUMMARY OF THE INVENTION[0002]Soluble forms of Fibroblast Growth Factor Receptor 1 (FGFR1) have been shown to inhibit tumor cell growth in vitro and in vivo. See, e.g., U.S. Pat. No. 7,678,890. Combining an anti-cancer therapeutic molecule, such as a soluble form of FGFR1, with another anti-cancer therapeutic molecule, can result in antagonistic, additive, or synergistic effects on the efficacy of each of the anti-cancer therapeutics.[0003]The inventors have discovered that administration of an FGFR1 ECD and docetaxel in a mouse xenograft model of non-small cell lung cancer shows synergistic anti-tumor activity of the therapeutic agents. In addition, the in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/71A61K31/337A61K33/24A61K31/365A61K31/513A61K31/282A61K39/395A61K31/704A61K38/17A61K31/519A61K33/243
CPCC07K14/71A61K38/179A61K31/337A61K33/24A61K31/519A61K2039/507A61K31/282A61K39/3955A61K31/704A61K31/365C07K2319/30A61K31/513A61K45/06A61K38/38A61K31/4745A61K31/475A61K31/555A61K31/7048A61P35/00A61K33/243A61K2300/00
Inventor LONG, LIBRENNAN, THOMAS
Owner FIVE PRIME THERAPEUTICS
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