On November 15, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of 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, NOV 15, 2024, View Source [SID1234648437]). Of significance, the CheckMate -8HW trial results showed reduction in the risk of disease progression or death by 79% (HR: 0.21; 95% CI: 0.14-0.32; p<0.0001) compared to chemotherapy in this patient population. The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the recommendation and make their decision.

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"Approximately 5-7% of metastatic colorectal cancer patients have dMMR or MSI-H tumors, and current treatment options often do not provide sufficient benefit," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "This is the first dual checkpoint inhibitor treatment for first-line metastatic colorectal cancer, delivering a transformative benefit for MSI-H/dMMR patients in this population. We are focused on bringing Opdivo plus Yervoy to these patients in the European Union and look forward to EC’s upcoming decision."

The positive opinion 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 Type II variation application, which was validated by 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) compared to the investigator’s choice of chemotherapy as assessed by Blinded Independent Central Review. In addition to the risk of disease progression or death the results noted, 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.

In October 2024, it was announced that Opdivo plus Yervoy also demonstrated a statistically significant and clinically meaningful improvement in the dual endpoint of PFS per BICR compared to Opdivo monotherapy across all lines of therapy. The study is ongoing to assess various secondary endpoints, including overall survival (OS).

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

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 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 firstline setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy.

CheckMate-8HW has also met its other dual primary point of PFS per BICR Opdivo plus Yervoy compared to Opdivo across all lines therapy in randomized subjects with centrally confirmed MSI-H/dMMR mCRC at the second interim analysis in September 2024, and data disclosure is planned for an upcoming medical conference. 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.