Bayer and Bristol-Myers Squibb Partner to Advance 'Targeted + Immunotherapy' Combination of Stivarga and Opdivo for Microsatellite Stable Metastatic Colorectal Cancer

July 19, 2019/Bio ValleyBIOON/--Bayer(Bayer), Bristol-Myers Squibb (BMS), and Ono Pharmaceutical (ONO) recently announced jointly that the three companies have signed a clinical collaboration agreement to evaluate Bayer’s multi-kinase inhibitor Stivarga (regorafenib) with Bristol-Myers Squibb/Ono Pharmaceutical’s PD-1TumorThe Opdivo (Opdivo, generic name: nivolumab) immunotherapy combination regimen is used for the treatment of patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC), which is the most common type of mCRC. Further terms of this clinical collaboration were not disclosed.

In the pivotal Phase III CORRECT study in mCRC, Stivarga as monotherapy demonstrated an overall survival benefit compared with placebo, and retrospective analyses of the study showed activity irrespective of microsatellite status, although observed responses were limited. Despite progress in the treatment of colorectal cancer (CRC), including effective immuno-oncology (I-O) therapies for certain CRC subgroups, approximately 95% of patients with mCRC have microsatellite-stable (MSS) tumors.Tumor, the role of I-O monotherapy is limited in this patient population. Therefore, there remains a high demand for other treatment regimens, including combination therapies.

Early data on the combination of Stivarga and Opdivo are encouraging. In a Phase Ib, investigator-sponsored study in Japan named REGONIVO (NCT03406871, EPOC1603),Clinical TrialIn China, the combination of Stivarga and Opdivo demonstrated promising preliminary efficacy in treating microsatellite stable (MSS) gastric cancer (GC) and colorectal cancer (CRC). The study enrolled a total of 50 patients, including 25 with GC and 25 with CRC. Among the CRC patients, one had microsatellite instability-high (MSI-H) disease, while the remaining were MSS. All patients had previously received standard therapies, with a median of 3 prior treatment regimens (range: 2–8).

The results showed a median treatment duration of 6.1 months. The overall objective response rate (ORR) was 40%, with an ORR of 44% in gastric cancer (GC) patients and 36% in colorectal cancer (CRC) patients. Excluding one patient with MSI-H CRC, the ORR in patients with MSS-type CRC remained as high as 33%. Among seven GC patients who had previously received PD-1 or PD-L1 inhibitors, three achieved partial response. The median progression-free survival (PFS) for the overall population was 6.3 months, with 5.8 months in GC patients and 6.2 months in CRC patients. Detailed data from this study were presented at the 2019 American Society of Clinical OncologyTumorpresented at the American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract No.: 2522）。

Bayer Pharmaceuticals DivisionTumorScott Z. Fields, M.D., Head of Development, stated, “The data observed in the REGONIVO study help to further explore the combination of Stivarga and Opdivo in patients with colorectal cancer. Stivarga has already demonstrated its efficacy and favorable safety profile as a third-line monotherapy. We are pleased to initiate this clinical collaboration to evaluate the combination therapy and hope to provide additional therapeutic benefits for patients.”

The active pharmaceutical ingredient of Stivarga is regorafenib, an oral multi-kinase inhibitor that effectively blocks pathways involved in tumor angiogenesis (VEGFR-1, -2, -3, TIE2), tumorigenesis (KIT, RET, RAF-1, BRAF), and tumor metastasis (VEGFR-3, PDGFR, FGFR),TumorMultiple protein kinases, including colony-stimulating factor 1 receptor (CSF1R). To date, Stivarga has been approved in more than 90 countries worldwide, including the United States, the European Union, China, and Japan, for the treatment of metastatic colorectal cancer (mCRC). The drug has also been approved in more than 80 countries globally for the treatment of metastatic gastrointestinal stromal tumors (GIST) and as second-line therapy for hepatocellular carcinoma (HCC).

Opdivo belongs to the PD-(L)1 class of cancer immunotherapies, which is currently the most prominent category of cancer immunotherapy. It aims to harness the body’s own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death, and is effective in treating multiple typesTumorpotential. Opdivo was approved in July 2014, becoming the first PD-1 immune checkpoint inhibitor to receive regulatory approval globally. Ono Pharmaceutical Co., Ltd is the original developer of Opdivo; in 2011, it entered into a collaboration with Bristol-Myers Squibb, granting Bristol-Myers Squibb the rights to develop and commercialize Opdivo in all regions except Japan, South Korea, and Taiwan. To date, the drug has been approved in 65 countries worldwide and has become an important treatment option for various types of cancer. (Bioon.com)

Original Source:Bayer, Bristol-Myers Squibb and Ono Pharmaceutical enter into a clinical collaboration agreement to investigate Stivarga® (regorafenib) and Opdivo® (nivolumab) as combination therapy in patients with colorectal cancer