Nivolumab Plus Low-Dose Ipilimumab Generates Long-term Benefit in Metastatic Colorectal Cancer

The 4-year follow-up results from the phase 2 CheckMate 142 study confirm the long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with microsatellite instability (MSI)-high/mismatch repair (MMR)-deficient metastatic colorectal cancer, with no new safety signals.

The ongoing, non-randomized, phase 2 trial enrolled 119 patients across 28 sites in 8 countries. All patients were given nivolumab 3 mg/kg and ipilimumab 1mg/kg by intravenous infusion once every 3 week for 4 doses, followed by nivolumab alone once every 2 weeks. Treatment continued until disease progression, discontinuation due to toxicity, death, withdrawal of consent, or the end of the study. While dose interruptions for treatment-related adverse events were permitted, dose modifications were not. The primary end point was objective response rate (ORR).

In the initial results, with a median follow-up duration of 13.4 months, nivolumab plus ipilimumab showed encouraging results in response rates, progression-free survival (PFS), 12-month overall survival (OS), tolerability, and key patient-reported outcomes.

In the 4-year follow-up data, the median follow-up duration was 50.9 months, with a median duration of therapy of 24.9 (95% confidence interval [CI], 15.8 to 33.2) months. The ORR increased from 55% (95% CI, 45% to 64%) in the initial results to 65% (95% CI, 55% to 73%) and the disease control rate was 81% (95% CI, 72% to 87%) in the current follow-up. Complete response increased from 3% in the initial results to 13%.

In the current follow-up, there was a partial response seen in 52% of patients and stable disease in 21%. At the time of data cut-off, 48% of patients had ongoing responses. Median time to response was 2.8 months. Median duration of response, median PFS, and median OS were not reached. The 48-month rate of PFS was 53% and the 48-month rate of OS was 71%.

Grade 3/4 treatment-related adverse events were seen in 32% of patients, with 13% of patients discontinuing treatment due to any grade of treatment-related adverse events. No new safety signals were observed from the initial results.

The study authors noted that there was “the deepening of responses over time,” and that “patients continued to experience improved health-related quality of life with long-term follow-up” in this study. The authors concluded that their follow-up results “support the use of this dual immune checkpoint inhibitor combination as a standard of care for these patients.”

Sources:

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

Overman M, Lonardi S, Wong KYM, et al. Durable clinical benefit with nicolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36(8):773-779. doi:10.1200.JCO.2017.76.9901