Bristol Myers Squibb's Opdivo-Yervoy combination immunotherapy approved in China

According to the Zhītōng Finance APP, on October 14th, Bristol Myers Squibb (BMY.US) announced that its "dual immune combination therapy" of Nivolumab combined with Ipilimumab has been approved by the National Medical Products Administration (NMPA) of China for the first-line treatment of unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer patients. According to Bristol Myers Squibb's press release, this is the first approval of this indication globally and marks the "global first launch" of the company's new drug indication in China.

Colorectal cancer (CRC) is a malignant tumor that occurs in the colon or rectum, both of which are part of the human digestive system. When proteins responsible for repairing mismatch errors during DNA replication are missing or non-functional, a dMMR phenotype occurs, leading to MSI-H tumors. Public data shows that approximately 5% to 7% of metastatic colorectal cancer patients have dMMR or MSI-H tumors, and they are less likely to benefit from traditional chemotherapy, usually with a poorer prognosis.

Ipilimumab is a CTLA-4 antibody, and Nivolumab is a PD-1 inhibitor. In March 2024, this dual immune therapy combination was included in the breakthrough therapy category by the Center for Drug Evaluation (CDE). In the same month, this combination therapy was granted priority review by the CDE for first-line treatment of colorectal cancer. This is also the indication for which this combination therapy has been approved this time.

According to Bristol Myers Squibb, this approval is based on the results of the CheckMate-8HW study. In January 2024, Bristol Myers Squibb orally presented the latest data from this study at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. This was a phase 3 randomized, open-label study that evaluated the efficacy of Nivolumab combined with Ipilimumab (dual immune combination therapy group) compared to Nivolumab monotherapy or investigator's choice of chemotherapy (mFOLFOX-6 or FOLFIRI regimen, with or without bevacizumab or cetuximab) in the treatment of MSI-H or dMMR phenotype metastatic colorectal cancer patients. Approximately 830 patients were randomly assigned to the Nivolumab monotherapy group, Nivolumab combined with Ipilimumab group, or investigator's choice of chemotherapy group.

According to Blind Independent Central Review (BICR) assessment, the dual immune combination therapy showed a significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS): compared to chemotherapy, in first-line treatment, for patients with MSI-H/dMMR phenotype mCRC confirmed by central laboratory testing, there was a 79% reduction in the risk of disease progression or death.

Furthermore, the improvement in PFS in the dual immune combination therapy group began around three months and remained consistent. The median PFS for the combination therapy group has not been reached, while it was 5.9 months for the chemotherapy group. Consistent PFS benefits were observed in all pre-specified subgroups, including patients with KRAS or NRAS mutations, as well as patients with liver, lung, or peritoneal metastases at baseline. The safety profile of the combination therapy was consistent with previously reported data, manageable within the established study protocol, and no new safety signals were identified