Nivolumab plus ipilimumab deemed tolerable in non-small cell lung cancer patients, with notable improvements in safety.
The combination of nivolumab plus ipilimumab as a first-line treatment showed a tolerable safety profile and promising clinical activity in patients with advanced non-small cell lung cancer (NSCLC).
In the open-label, multi-cohort phase 1 CheckMate 012 trial, the cohorts were enrolled at 8 academic centers in the United States. Participants were 18 or older with histologically or cytologically confirmed recurrent stage 3b or stage 4, chemotherapy-naïve NSCLC.
The study was conducted between May 15, 2014, and March 25, 2015. Patients were randomized 1:1:1 by an interactive voice response system to receive either 1 mg/kg nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks; nivolumab 3 mg/kg every 2 weeks plus 1 mg/kg ipilimumab every 12 weeks; or nivolumab 3 mg/kg every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks until disease progression, unacceptable toxicities, or withdrawal of consent.
Seventy-eight patients received nivolumab every 2 weeks plus ipilimumab every 12 weeks (n=38), or nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=40). There was 1 patient in the ipilimumab every 6 weeks cohort who was excluded before treatment.
At data cut-off on January 7, 2016, there were 29 (76%) patients in the ipilimumab every 12 weeks cohort, and 32 (82%) patients in the ipilimumab every 6 weeks cohort who had discontinued treatment.
The most common grade 3 or 4 treatment-related adverse events (AEs) were increased lipase, pneumonitis, adrenal insufficiency, and colitis. The AEs prompted treatment discontinuation in 4 patients in the 12 weeks arm, and 5 patients in the 6 weeks arm. There were no treatment-related deaths reported in the trial.
In the ipilimumab every 12 weeks cohort, confirmed objective response was achieved in 19 patients (47% [95% CI 31-64)], compared with 15 patients in the ipilimumab every 6 weeks cohort (38% [95% CI 23-55)].
The median duration of response was not reached in either cohort, with median follow-up times of 12.8 months in the ipilimumab every 12 weeks cohort, and 11.8 months in the ipilimumab every 6 weeks cohort.
For patients with PD-L1 of 1% or greater, confirmed objective responses were achieved in 12 of 21 patients in the ipilimumab every 12 weeks cohort, and 12 of 23 patients in the ipilimumab every 6 weeks cohort.
The findings, published in The Lancet, revealed that first-line nivolumab plus ipilimumab had a tolerable safety profile in NSCLC, and showed encouraging clinical activity characterized by a high response rate and durable response.
The authors concluded that the results of the study are the first suggestion of improved benefit from the nivolumab combination compared with anti-PD-1 monotherapy in NSCLC patients, which further supports additional assessment of the combination in a phase 3 study.