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Combination therapy for treatment of cancer

A technology for treating cancer, applied in drug combinations, cancer antigen components, antibody medical components, etc.

Inactive Publication Date: 2018-02-16
ONCOMED PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

RSPO proteins are known to activate β-catenin signaling similar to Wnt signaling, however, the relationship between RSPO proteins and Wnt signaling is still under investigation

Method used

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  • Combination therapy for treatment of cancer
  • Combination therapy for treatment of cancer
  • Combination therapy for treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0330] Activity of anti-RSPO3 antibody OMP-131R010 in combination with chemotherapeutic agents in an in vivo ovarian tumor model

[0331] The OncoMed xenograft model described herein was established at OncoMed Pharmaceutical Co., Ltd. from minimal passage patient-derived tumor specimens. Tumor specimens are examined by a pathologist and classified into specific tumor types. OncoMed follows these classifications unless further analysis is performed on any particular tumor and a reclassification is deemed necessary.

[0332] Xenograft OMP-OV19 ovarian tumor cells (1×10 5 cells) were injected subcutaneously into NOD / SCID mice. Tumors were allowed to grow for 39 days until they reached approximately 120mm 3 average volume. Tumor-bearing mice were randomly divided into four groups (n=8 to 9 animals / group). Tumor-bearing mice were treated with (i) control antibody, (ii) paclitaxel alone, (iii) anti-RSPO3 antibody OMP-131R010 plus paclitaxel or (iv) anti-RSPO3 antibody OMP-131R0...

Embodiment 2

[0334] Activity of anti-RSPO3 antibody OMP-131R010 combined with chemotherapeutic agents in an in vivo model of lung cancer

[0335] Xenograft OMP-LU77 lung tumor cells (5×10 4cells) were injected subcutaneously into NOD / SCID mice. Tumors were allowed to grow for 34 days until they reached approximately 125mm 3 average volume. Tumor-bearing mice were randomly divided into four groups (n=9 animals / group). Tumor-bearing mice were treated with (i) control antibody, (ii) paclitaxel alone, (iii) anti-RSPO3 antibody OMP-131R010 plus paclitaxel or (iv) anti-RSPO3 antibody OMP-131R010 plus paclitaxel administered on the same day (wherein the antibody was administered 2 days before paclitaxel). Antibody was dosed at 25 mg / kg and paclitaxel was dosed at 20 mg / kg, both agents were administered every 3 weeks. Tumor volumes were measured on indicated days after treatment. The results are shown in figure 2 . As seen in the ovarian tumor model of Example 1, staggered administration ...

Embodiment 3

[0337] Activity of anti-RSPO3 antibody OMP-131R010 combined with chemotherapeutic agents in an in vivo model of colorectal cancer

[0338] Xenograft OMP-C8 colon tumor cells (5×10 4 cells) were injected subcutaneously into NOD / SCID mice. OMP-C8 colon tumor cells contained an inactivating mutation in the APC gene and expressed low levels of RSPO3 (data not shown). Tumors were allowed to grow for 23 days until they reached approximately 100mm 3 average volume. Tumor-bearing mice were randomly divided into four groups (n=9 animals / group). Tumor-bearing mice were treated with: (i) control antibody, (ii) nab-paclitaxel (ABRAXANE) alone, (iii) anti-RSPO3 antibody OMP-131R010 plus nab-paclitaxel administered on the same day, (iv) anti-RSPO3 antibody OMP-131R010 plus nab-paclitaxel (where the antibody is administered 2 days before paclitaxel), (v) fluorouracil and irinotecan, (vi) anti-RSPO3 antibody administered on the same day OMP-131R010 plus fluorouracil and irinotecan, or (v...

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Abstract

Described herein are combination therapies for the treatment of cancer and other diseases. In one aspect, the methods described herein for the treatment of cancer and other diseases comprise administering a RSPO-LGR pathway inhibitor in combination with a mitotic inhibitor. The present invention relates to methods of treating cancer comprising administering to a subject a therapeutically effectiveamount of an RSPO-LGR pathway inhibitor, such as an antiRSP03 antibody or anti-LGR5 antibody. In certain embodiments, the methods further comprise administration of a mitotic inhibitor to the patient. In certain embodiments the RSPO-LGR pathway inhibitor is administered about 1 day, about 2 days, or about 3 days prior to the mitotic inhibitor.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to US Provisional Application No. 62 / 086,435, filed December 2, 2014, and US Provisional Application No. 62 / 210,545, filed August 27, 2015, each of which is incorporated herein by reference in its entirety. technical field [0003] Combination therapies for the treatment of cancer and other diseases are described herein. In one aspect, the methods described herein for treating cancer and other diseases comprise administering an inhibitor of the RSPO-LGR pathway in combination with an inhibitor of mitosis. Background technique [0004] The R-spinin (RSPO) protein family is conserved in vertebrates and comprises four members, RSPO1, RSPO2, RSPO3 and RSPO4. These proteins have various names including apical plate-specific spinin, hPWTSR (hRSPO3), THS2D (RSPO3), Cristin 1-4 and Futrin 1-4. RSPO is a small secreted protein that collectively shares approximately 40% to 60% se...

Claims

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Application Information

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IPC IPC(8): A61K39/395
CPCA61K31/337A61K45/06A61K31/357A61K31/427A61K31/475C07K16/18A61K2039/505A61P35/00A61K39/0011A61K2300/00A61K39/385A61K39/39558A61K39/39591A61K39/44A61K2039/507C07K2317/22C07K2317/24C07K2317/30C07K2317/32
Inventor 奥斯丁·格尼W-C·延蒂莫西·查尔斯·霍伊
Owner ONCOMED PHARMA
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