Safety of Nivolumab plus Low-Dose Ipilimumab in Previously Treated Microsatellite Instability-High Mismatch Repair-Deficient Metastatic Colorectal Cancer

Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 https://kelleysbookkeeping.com/tax-formula-to-determine-adusted-gross-income-and/ to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life.

• Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression.
• Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population.
• Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile.
• Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable.
• Median duration of response was not reached; most responses (94%) were ongoing at data cutoff.

Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC. Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression.

Patients and methods

Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). The results confirm Durable Clinical Benefit With Nivolumab Plus Ipilimumab In Dna Mismatch Repair long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC.