FDA Approves Nivolumab Plus Low-Dose Ipilimumab for Second-Line Treatment of MSI-H/dMMR Metastatic Colorectal Cancer
Today, 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 has been granted under accelerated approval based on overall response rate and duration of response.
This approval was based on data from the ongoing phase II CheckMate-142 study, which is evaluating the nivolumab/ipilimumab combination in patients with MSI-H or dMMR metastatic colorectal cancer previously treated with a fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. The application was granted Priority Review and Breakthrough Therapy designation by the FDA.
Study Details
The nivolumab-plus-ipilimumab cohort of the CheckMate-142 trial enrolled MSI-H/dMMR metastatic 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 nivolumab maintenance 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-ipilimumab cohort of CheckMate-142, 86% of patients received all 4 doses of nivolumab plus ipilimumab. Ipilimumab was discontinued in 13% of patients and delayed in 45% of patients due to an adverse reactions. Serious adverse reactions occurred in 47% of patients.
The most frequent serious adverse reactions reported in at least 2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. The most common adverse reactions (reported in at least 20% of patients) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%).
“Metastatic colorectal cancers with dMMR or MSI-H biomarkers can be difficult to treat, and some patients may need additional options,” said Heinz-Josef Lenz, MD, FACP, 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. “The FDA’s approval of an I-O/I-O [dual immuno-oncology] combination provides us with an encouraging approach to address this challenging disease in patients who have [had disease progression] following treatment with three standard chemotherapy options.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
