Results announced for Checkmate trial evaluating Opdivo and Yervoy.

Bristol-Myers Squibb Company 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 (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).

With a median of 13.4 months of follow-up, the primary endpoint of objective response rate (ORR) 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 (OS) rate at one year was 85% (95% CI: 77.0 to 90.2), and median OS was not yet reached. Grade 3-4 treatment-related adverse events (TRAEs) 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.

These CheckMate -142 data from Abstract #553 will be featured today in an oral presentation at the 2018 Gastrointestinal Cancers Symposium in San Francisco, Calif., and simultaneously published in the Journal of Clinical Oncology.

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 (MSI-H) and non-MSI-H colorectal cancer. The primary endpoint is investigator-assessed objective response rate (ORR) using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other key endpoints include duration of response (DOR), overall survival (OS), progression-free survival (PFS), disease control rate (DCR), ORR per blinded independent central review (BICR), patient reported outcomes and safety. 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 (TRAEs) 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.