Study data published in the Annals of Oncology confirm the long-term clinical benefits of nivolumab plus low-dose ipilimumab for previously treated patients with microsatellite instability high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
CheckMate 142 is an ongoing phase 2 trial (ClinicalTrials.gov Identifier: NCT02060188) of adult patients with histologically confirmed recurrent or mCRC classified as MSI-H and/or dMMR. Enrollment began in 2014 at 32 medical centers in Australia, Belgium, Canada, France, Ireland, Italy, Spain, and the United States. Eligible patients had disease progression on or after therapy or were intolerant to at least 1 prior systemic treatment. Per study protocol, patients received intravenous nivolumab 3 mg/kg (60-minute infusion) and low-dose ipilimumab 1 mg/kg (90-minute infusion) once every 3 weeks for 4 total doses, followed by nivolumab 3 mg/kg every 2 weeks until disease progression, discontinuation, or study conclusion.
The primary endpoint was investigator-assessed objective response rate per the Response Evaluation Criteria in Solid Tumours guidelines. Tumors were assessed for partial or complete response using computed tomography or magnetic resonance imaging less than or equal to 28 days prior to the first dose, every 6 weeks for 24 weeks, and every 12 weeks thereafter. Adverse events were assessed throughout treatment and for at least 100 days after treatment cessation.
Overall, 119 patients with MSI-H/dMMR mCRC were enrolled and treated. Median age at baseline was 58 (range, 21-88) years; 58% were men; 92% were White; and 76% had at least 2 prior lines of treatment. Median (range) follow-up duration was 50.9 (46.9-62.7) months; median treatment duration was 24.9 months. Per investigator assessment, objective response was achieved in 65% of patients (95% CI, 45%-64%) by the conclusion of follow-up. Disease control for at least 12 weeks was achieved in 81% of patients (95% CI, 72%-87%). Median (range) time to response was 2.8 (1.1-37.1) months from first infusion. Overall, 13% of patients had a complete response; 52% had partial response; 21% had stable disease; and 12% had progressive disease.
No new safety signals or treatment-related deaths were observed during follow-up. Treatment-related adverse events were reported by 85% of patients, the most common of which were diarrhea (27%) and pruritis (21%). Discontinuation due to adverse events occurred in 13% of patients.
These long-term follow-up data support the continued clinical benefit of nivolumab plus low-dose ipilimumab in previously treated patients with MSI-H/dMMR mCRC.
Study limitations include the lack of a comparator group; further study with a randomized design is underway.
“Nivolumab plus low-dose ipilimumab provided durable clinical benefit over 4 years of follow-up, characterized by high response rates, low rates of disease progression, and long-term survival benefit,” the study authors wrote.
Disclosure: This research was supported by Bristol-Myers Squibb. Please see the original reference for a full list of disclosures.
André T, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. Published online June 25, 2022. doi:10.1016/j.annonc.2022.06.008