On July 11, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) plus low-dose ipilimumab (Yervoy) for the treatment of adult and pediatric patients aged 12 years and older with microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Approval for this indication was based on data from the ongoing phase II CheckMate-142 study and has been granted under accelerated approval based on overall response rate and duration of response. The application was granted Priority Review and Breakthrough Therapy designation by the FDA.
The nivolumab-plus-ipilimu-mab cohort of the CheckMate-142 trial enrolled MSI-H/dMMR meta-static colorectal cancer patients who had received at least one prior line of therapy for metastatic disease, and efficacy was analyzed for both patients who had received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan (82 of the total 119 patients), as well as for all enrolled patients.
Among the 82 patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, 46% (95% confidence interval [CI] = 35%–58%; n = 38/82) responded to treatment with nivolumab plus ipilimumab, as assessed by an independent radiographic review committee.
The percentage of these patients with a complete response was 3.7% (n = 3/82), and the percentage of patients with a partial response was 43% (n = 35/82). Among these 38 responders, the median duration of response was not reached (range = 1.9–23.2+ months); 89% of those patients had responses of 6 months or longer, and 21% had responses of 12 months or longer. This trial is ongoing.
The recommended dosing schedule includes the nivolumab-plus-ipilimumab combination (nivolumab at 3 mg/kg, administered as an intravenous infusion over 30 minutes, followed by ipilimumab at 1 mg/kg, administered as an intravenous infusion over 30 minutes, on the same day, every 3 weeks for 4 doses), followed by nivolumabmaintenance therapy (240 mg, administered as an intravenous infusion over 30 minutes every 2 weeks) after completion of 4 doses of the combination until disease progression or unacceptable toxicity.
In the nivolumab-plus-ipilimu-mab cohort of CheckMate-142, 86% of patients received all 4 doses of nivolu-mab plus ipilimumab. Ipilimumab was discontinued in 13% of patients and delayed in 45% due to an adverse reaction. Serious adverse reactions occurred in 47% of patients. ■