Nivolumab, Ipilimumab Combo Approved by FDA for MSI-H/dMMR Colorectal Cancer

JULY 11, 2018
Jason M. Broderick
The FDA has granted an accelerated approval to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

The approval is based on results from a cohort of 119 patients with MSI-H or dMMR mCRC treated with the combination in the phase II CheckMate-142 study. In this cohort, 82 patients received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and the overall response rate (ORR) was 46% (95% CI, 35-58) among these patients.1 Among the 38 responders, there were 3 complete responses (CRs) and 35 partial responses (PRs). The median duration of response (DOR) was not reached (range, 1.9-23.2+ months). Eighty-nine percent of the responders had a response of ≥6 months, with 21% having a response ≥12 months.

Among all 119 patients, the ORR was 49% (95% CI, 39-58). Among the 58 responders, there were 5 CRs and 53 PRs. The median DOR was not reached (range, 1.9-23.2+ months), with 83% of responders having a response ≥6 months and 19% having a response ≥12 months. Fifty-one of the 58 responses were ongoing at the data cutoff.  

“Metastatic colorectal cancers with dMMR or MSI-H biomarkers can be difficult to treat and some patients may need additional options,” Heinz-Josef Lenz, MD, L. Terrence Lanni Chair in Gastrointestinal Cancer Research, Keck School of Medicine of University of Southern California and principal investigator of the study at USC Norris Comprehensive Cancer Center, said in a statement.

“The FDA’s approval of an I-O/I-O combination provides us with an encouraging approach to address this challenging disease in patients who have progressed following treatment with three standard chemotherapy options,” added Lenz.

Data from the trial were published in the Journal of Clinical Oncology in March 2018.2 The 119 patients in the combination cohort were treated with nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab at 3 mg/kg every 2 weeks. The median patient age was 58 years (range, 21-88), 59% of patients were male, and 92% were white. Forty-five percent of patients had an ECOG performance status of 0, with the remaining 55% having a status of 1.

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