Bristol-Myers Squibb Co. announced new data from a cohort of the phase II CheckMate -142 trial evaluating Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of patients with DNA mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer.
With a median of 13.4 months of follow-up, the primary endpoint of objective response rate per investigator assessment was 55% (95% CI: 45.2 to 63.8). Responses were durable, with median duration of response not yet reached and 94% of responses ongoing at time of data cutoff.
The overall survival rate at one year was 85% (95% CI: 77.0 to 90.2), and median OS was not yet reached. Grade III-IV treatment-related adverse events occurred in 32% of patients receiving the Opdivo plus Yervoy combination. Patients received mCRC combination dosing of Opdivo (3 mg/kg) plus Yervoy (1 mg/kg) every three weeks for four doses, followed by Opdivo (3 mg/kg) every two weeks until disease progression, death or unacceptable toxicity.
CheckMate -142 is an international phase II, multi-cohort, open-label, non-comparative trial of Opdivo, or Opdivo combinations, in recurrent and metastatic microsatellite instability-high and non-MSI-H colorectal cancer.
The primary endpoint is investigator-assessed objective response rate using the Response Evaluation Criteria In Solid Tumors version 1.1. Other key endpoints include duration of response, overall survival, progression-free survival, disease control rate, ORR per blinded independent central review, patient reported outcomes and safety.
The Opdivo plus Yervoy combination cohort included 119 patients with a median follow-up of 13.4 months. At the time of data cutoff (July 2017) median PFS was not yet reached, the 12-month PFS rate was 71% (95% CI: 61.4 to 78.7) and the rate of disease control lasting at least 12 weeks was 80%. Investigator-assessed responses were observed irrespective of tumor BRAF or KRAS mutation status, tumor PD-L1 expression or clinical history of Lynch syndrome. Statistically significant and clinically meaningful improvements were observed in key patient reported outcomes, including symptoms, functioning and quality of life.
Treatment-related adverse events of any grade occurred in 73% of patients, with the most common being diarrhea (22%), fatigue (18%), and pruritus (17%).
Select TRAEs of potential immunologic etiology resolved in most patients (range, 71%−96%), except for endocrine TRAEs, which resolved in 40% of patients. No new safety signals or treatment-related deaths were reported. Study drug-related adverse events led to a 13% discontinuation rate, and among these patients the ORR was 63%, which was consistent with that of the overall population.
Opdivo as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.
This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
