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

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 the protein responsible for repairing mismatch errors is missing or non-functional during DNA replication, a dMMR phenotype appears, leading to MSI-H tumors. Public data shows that approximately 5% to 7% of metastatic colorectal cancer patients have dMMR or MSI-H tumors, as they are unlikely to benefit from traditional chemotherapy, usually resulting in a poorer prognosis.

Ipilimumab is a CTLA-4 antibody, while nivolumab is a PD-1 inhibitor. In March 2024, this dual immune therapy combination was included as a breakthrough therapy by the Center for Drug Evaluation (CDE). The same month, this dual immune therapy combination was granted priority review by the CDE for first-line treatment of colorectal cancer, which is also the indication for which this combination therapy was approved.

According to Bristol-Myers Squibb, this approval was 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 evaluating the efficacy of nivolumab in combination with ipilimumab (dual immune combination therapy group), compared to nivolumab monotherapy or investigator's choice of chemotherapy regimen (mFOLFOX-6 or FOLFIRI regimen, with or without bevacizumab or cetuximab) in the treatment of mCRC patients with MSI-H or dMMR phenotype. Approximately 830 patients were randomly assigned to nivolumab monotherapy, nivolumab in combination with ipilimumab, or investigator's choice of chemotherapy regimen group.

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

Furthermore, the PFS improvement in the dual immune combination therapy group began around three months and remained consistent. The median PFS of 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 predefined subgroups, including patients with KRAS or NRAS mutations, as well as those with baseline liver, lung, or peritoneal metastases. The safety profile of the combination therapy remains consistent with previously reported data, controlled under the established study protocol, with no new safety signals identified.