The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Bristol Myers Squibb’s (BMS) Opdivo (nivolumab) and Yervoy (ipilimumab) combination therapy 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). This decision marks a significant advancement in the treatment landscape for this specific subset of colorectal cancer patients.
The CHMP's positive opinion stems from the results of the Phase III, open-label CheckMate -8HW trial. This trial demonstrated a significant 79% reduction in the risk of disease progression or mortality compared to chemotherapy. The randomized trial compared the efficacy of Opdivo in combination with Yervoy against Opdivo alone or the investigator’s choice of chemotherapy.
CheckMate -8HW Trial Details
The CheckMate -8HW trial randomized 839 patients to receive either Opdivo monotherapy, the Opdivo and Yervoy combination, or chemotherapy. The study's dual primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review (BICR). The combination therapy demonstrated a statistically significant improvement in PFS compared to chemotherapy. The safety profile of the dual immunotherapy combination was consistent with previously reported data, with no new safety signals identified.
Further data presented in October 2024 indicated that the combination therapy also significantly improved PFS compared to Opdivo monotherapy across all lines of therapy. The ongoing CheckMate -8HW study continues to evaluate secondary endpoints, including overall survival.
Clinical Significance
Approximately 5% to 7% of patients with metastatic colorectal cancer have dMMR or MSI-H tumors. Current treatment options often provide limited benefit for these patients. According to Dana Walker, vice-president and global program lead for gastrointestinal and genitourinary cancers at Bristol Myers Squibb, this combination represents "the first dual checkpoint inhibitor treatment for first-line metastatic colorectal cancer, delivering a transformative benefit for MSI-H/dMMR patients in this population."
The European Commission (EC) is now reviewing the CHMP’s recommendation and will make a final decision regarding approval within the European Union (EU). If approved, this combination therapy could offer a new standard of care for patients with MSI-H/dMMR mCRC, addressing a significant unmet medical need.
