Bristol-Myers Squibb (BMS) said today that the combination of its marketed cancer immunotherapies Opdivo (nivolumab) plus a low dose of Yervoy (ipilimumab) showed durable clinical benefit in a Phase II trial as a first-line treatment in patients with microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).
BMS announced data from its CheckMate-142 trial (NCT02060188) showing that with a median follow-up of 13.8 months, the primary endpoint of investigator-assessed objective response rate (ORR) was 60%, with a 7% complete response (CR) rate. At the time of data cutoff, 82% of responding patients had ongoing responses, of whom 74% had responses lasting more than six months—though BMS added that the median duration of response (DOR) had not yet been reached.
The Opdivo-Yervoy combination demonstrated a disease control rate (DCR) of 84% at 12 weeks or longer. At one-year follow-up, the median overall survival (OS) rate was 83%, and the progression-free survival (PFS) rate was 77%. Median OS and median PFS had not yet been reached.
“This is the first and only immuno-oncology combination to show a clinical benefit in this hard-to-treat patient population, further validating our precision medicine approach,” Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, BMS, said in a statement.
CheckMate-142 is an international Phase II, multi-cohort, open-label, non-comparative trial assessing Opdivo or Opdivo combinations, in recurrent or metastatic MSI-H and non-MSI-H colorectal cancer. The trial’s primary endpoint is investigator-assessed ORR using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other key endpoints included DOR, OS, PFS, DCR, ORR per blinded independent central review, patient reported outcomes, and safety.
The Opdivo plus low-dose Yervoy first-line cohort included 45 patients (51% male, with a median age of 66 years) with a median follow-up of 13.8 months. Any grade treatment-related adverse events (TRAEs) included pruritus (24%), hypothyroidism (18%), asthenia (16%), arthralgia (13%), increased lipase (11%), nausea (11%) and rash (11%). Grade 3-4 TRAEs were limited to hypothyroidism (2%) and asthenia (2%) and led to treatment discontinuation in one patient (2%).
BMS presented the data from CheckMate-142 (Abstract #LBA18) today in a proffered paper session at the European Society for Medical Oncology (ESMO) 2018 Annual Congress, being held October 19-23 in Munich, Germany.
“Today’s results from CheckMate -142 underscore the durability of Opdivo plus low-dose Yervoy in metastatic colorectal cancer patients whose tumors express MSI-H or dMMR biomarkers, and show the potential for this combination as a first-line treatment for these patients, who typically experience poor treatment outcomes,” added Heinz-Josef Lenz, M.D., FACP, associate director, Adult Oncology and co-leader, Gastrointestinal Cancers Program, Norris Comprehensive Cancer Center, University of Southern California.