The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of Opdivo (nivolumab) plus Yervoy (ipilimumab) for the treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC). This recommendation is based on the CheckMate-8HW trial, which demonstrated a significant reduction in the risk of disease progression or death compared to chemotherapy.
The CheckMate-8HW trial results showed a 79% reduction in the risk of disease progression or death (HR: 0.21; 95% CI: 0.14-0.32; p<0.0001) compared to chemotherapy in the MSI-H/dMMR mCRC patient population. The European Commission (EC) will now review the CHMP recommendation and make a final decision regarding approval for use in the European Union.
Clinical Significance
"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. She further stated, "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."
The positive CHMP opinion is grounded in data from the CheckMate-8HW trial, which were presented at medical congresses earlier in the year. The trial's data supported the company’s Type II variation application, validated by the EMA. The study highlighted a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to the investigator’s choice of chemotherapy, as assessed by Blinded Independent Central Review (BICR).
Safety and Efficacy
In addition to the significant reduction in the risk of disease progression or death, the safety profile for the dual immunotherapy combination of Opdivo and Yervoy was consistent with previously reported data. The safety profile was manageable with established protocols, and no new safety signals were identified.
In October 2024, Bristol Myers Squibb announced that Opdivo plus Yervoy also demonstrated a statistically significant and clinically meaningful improvement in PFS per BICR compared to Opdivo monotherapy across all lines of therapy. The CheckMate -8HW trial is ongoing to assess various secondary endpoints, including overall survival (OS).
