The combination of nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) continues to demonstrate significant and lasting clinical benefits in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (CRC) when used as a first-line treatment. The CheckMate-142 study's latest results, presented at the ASCO 2020 virtual annual meeting, reveal a deepening of response and sustained efficacy with longer follow-up.
Sustained Clinical Benefit
According to lead investigator Dr. Heinz-Josef Lenz, Co-Director of the Gastrointestinal Oncology Program at the University of Southern California Norris Comprehensive Cancer Center, the median duration of response, median progression-free survival (PFS), and median overall survival (OS) had not been reached after a median follow-up of 29 months. This suggests a substantial and durable benefit for patients receiving this immunotherapy doublet.
"Nivolumab and low-dose ipilimumab may represent a new first-line therapy option for patients with MSI-high and mismatch repair-deficient metastatic colorectal cancer," Dr. Lenz stated, highlighting the potential of this combination to address an unmet need in this patient population.
Addressing Unmet Needs
Patients with MSI-H or dMMR metastatic CRC often experience poor outcomes with standard first-line chemotherapy-based regimens. The nivolumab and ipilimumab combination had previously shown efficacy in pre-treated patients with MSI-H or dMMR metastatic CRC in the CheckMate-142 trial, leading to accelerated FDA approval for patients whose disease progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
Study Design and Results
The CheckMate-142 study is an ongoing, multicohort, nonrandomized phase 2 trial. Patients received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression or discontinuation. The study population consisted of 45 patients, with 38% having metastatic CRC with BRAF mutation, 22% with KRAS mutations, and 18% with Lynch syndrome. At data cutoff, 33% of the patients were still receiving treatment.
Between the earlier analysis at 13.8 months of follow-up and the current analysis at a median follow-up of 29 months, a majority of patients experienced a deepening of response. Approximately 84% of patients had a reduction in tumor burden from baseline. At 24 months, the PFS rate was 74%, and the OS rate was 79%.
The investigator-assessed objective response rate (ORR) increased from 60% at the 13.8-month follow-up to 69% at the 29-month follow-up. The complete response (CR) rate also improved, rising from 7% to 13%, with three additional patients achieving a complete response and one additional patient achieving a partial response since the previous data cutoff. The disease control rate (DCR) was 84% at the latest follow-up.
Safety Profile
The safety profile of nivolumab plus low-dose ipilimumab remained consistent with longer follow-up, and no new safety signals were reported. The regimen was well-tolerated, with 22% of patients experiencing grade 3 or 4 treatment-related adverse events, and only 7% discontinuing treatment due to these adverse events.
