Bristol Myers Squibb (BMS) announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Opdivo (nivolumab) combined with Yervoy (ipilimumab) as a first-line treatment. This treatment targets adult patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC). The CheckMate -8HW trial demonstrated substantial benefits for this patient population. Results revealed a 79% reduction in the risk of disease progression or death compared to standard chemotherapy regimens. This positive CHMP opinion is a significant milestone, paving the way for the European Commission (EC) to review the recommendation and issue a final decision regarding approval within the European Union.
This combination therapy represents a significant advancement, as it is the first dual checkpoint inhibitor approved for first-line treatment of metastatic colorectal cancer in this specific patient group. It addresses a significant unmet need, as current treatments often provide insufficient benefit to the approximately 5-7% of metastatic colorectal cancer patients with dMMR or MSI-H tumors. BMS anticipates a favorable EC decision and aims to make this treatment available to eligible patients in the EU.
The CHMP’s recommendation stems from the CheckMate -8HW trial, where Opdivo plus Yervoy exhibited clinically meaningful improvement in progression-free survival (PFS) compared to investigator’s choice of chemotherapy. The assessment was conducted by Blinded Independent Central Review (BICR). Furthermore, the combination therapy’s safety profile aligns with previously reported data. It appears manageable with established protocols, without new safety signals.
In another development, the combination therapy also demonstrated a statistically significant and clinically meaningful improvement in PFS (per BICR) compared to Opdivo monotherapy across all lines of therapy, as announced in October 2024. The CheckMate -8HW trial, a Phase 3 randomized, open-label study, enrolled 839 patients. It compared Opdivo plus Yervoy to Opdivo alone and investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with MSI-H or dMMR unresectable or metastatic colorectal cancer. The trial’s primary endpoints include PFS per BICR for the combination versus chemotherapy in the first-line setting and PFS for the combination versus Opdivo monotherapy across all treatment lines. Secondary endpoints, including overall survival, are still under evaluation. The trial successfully met its other dual primary endpoint of PFS per BICR for Opdivo plus Yervoy compared to Opdivo across all lines of therapy in patients with centrally confirmed MSI-H/dMMR mCRC in a second interim analysis conducted in September 2024. These results are slated for presentation at an upcoming medical conference.
Colorectal cancer (CRC), affecting the colon or rectum, is a prevalent global health concern. It’s the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths. dMMR occurs when DNA repair proteins are dysfunctional or absent, leading to MSI-H tumors. These tumors, present in roughly 5-7% of metastatic CRC cases, often respond poorly to conventional chemotherapy and are associated with a poor prognosis. BMS is dedicated to improving outcomes for cancer patients, aiming to develop innovative treatments that enhance quality of life and pursue the possibility of a cure. BMS leverages its expertise in immuno-oncology, personalized medicine, and data analysis to achieve these goals, approaching cancer from multiple perspectives.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
