On December 23, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC) (Press release, Bristol-Myers Squibb, DEC 23, 2024, View Source [SID1234649259]).

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"Colorectal cancer is the second leading cause of cancer death in Europe and patients are in need of new treatment options that delay disease progression. Approximately 5-7% of metastatic colorectal cancer patients have MSI-H/dMMR tumors and these patients are less likely to benefit from conventional chemotherapy and typically have poor prognosis outcomes," said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. "The EC’s decision to approve Opdivo plus Yervoy represents a significant milestone for this patient population in the European Union and underscores our commitment to advancing treatment options."

The decision is based on results from the CheckMate -8HW trial, which were presented at medical congresses earlier this year. These data formed the basis for the Company’s application to the European Medicines Agency (EMA). In the study, Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) and reduced the risk of disease progression or death by 79% compared to the investigator’s choice of chemotherapy as assessed by Blinded Independent Central Review (BICR). The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

This approval by the EC for Opdivo plus Yervoy for the first-line treatment of adult patients with MSI-H or dMMR unresectable or mCRC is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approval in colorectal cancer, Opdivo- based options are also approved for treatment of multiple tumor types in the EU.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

CheckMate -8HW and Select Efficacy and Safety Results

With a median follow-up of approximately 31.5 months, CheckMate -8HW trial results showed:

PFS (progression-free survival; a dual primary endpoint): Opdivo plus Yervoy reduced the risk of disease progression or death by 79%. Median PFS was not yet reached in the Opdivo plus Yervoy arm (95% CI: 38.4-NE) vs. 5.9 months in the chemotherapy arm (95% CI: 4.4-7.8). Consistent PFS benefit was observed across all pre-specified subgroups, including patients with KRAS or NRAS mutations, and those with baseline liver, lung, or peritoneal metastases.
Safety: The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23% of patients in the Opdivo plus Yervoy arm and 48% of patients in the chemotherapy arm. Any grade TRAE-related discontinuation was 17% in the Opdivo plus Yervoy arm and 32% in the chemotherapy arm.
About CheckMate -8HW

CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or the investigator’s choice of chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC).

839 patients were randomized to receive either Opdivo monotherapy ( Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W ), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first-line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. Further data disclosure is planned at The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place January 23, 2025, through January 25, 2025. The trial also evaluates several secondary safety and efficacy endpoints, including overall survival, which is ongoing.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors. These patients are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.