Nivolumab, Ipilimumab Combo Improves Colorectal Cancer Outcomes

Combination therapy found to increase anti-tumor activity among patients with metastatic colorectal cancer.

Bristol-Myers Squibb recently announced positive findings from the phase 2 CheckMate-142 clinical trial, which evaluated a combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), according to a press release.

Data from the trial were presented at the 2018 Gastrointestinal Cancers Symposium.

“These results demonstrate that Opdivo plus Yervoy provide durable clinical benefit in patients with dMMR or MSI-H metastatic colorectal cancer,” said Thierry André, MD, head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris. “The combination of Opdivo and Yervoy may represent an important advance for these distinct biomarker-defined patients, who historically have poorer outcomes compared to metastatic colorectal cancer patients whose tumors are mismatch repair proficient or microsatellite stable.”

Included in the study were 199 patients with dMMR or MSI-H mCRC who were treated with a combination of nivolumab 3-mg/kg plus ipilimumab 1-mg/kg every 3 weeks for 4 doses, followed by nivolumab 3-mg/kg every 2 weeks until progression, death, or toxicity.

The researchers found that the trial’s primary endpoint of objective response rate (ORR) was 55% at 12.4 months. The analysis also showed that the rate of disease control persisting longer than 12 weeks was 80% among these patients, according to the release.

Bristol-Myers said that the responses were long-lasting, with 94% of responses persisting at data cutoff; however, median duration of response has not yet been reached, according to the release.

Other key endpoints include duration of response, overall survival, progression-free survival, disease control rate, ORR per blinded independent central review, and patient-reported outcomes and safety.

The researchers noted that statistically significant improvements were achieved in patient-reported symptoms, functioning, and quality of life, according to the release.

Treatment-related adverse events occurred in 73% of patients, with diarrhea, fatigue, and pruritus being the most common. Only 13% of patients discontinued due to adverse events.

Bristol-Myers said that there were no new safety concerns or treatment-related deaths reported in the trial.

“The Opdivo and Yervoy combination has demonstrated efficacy across tumors in a broad range of patients, and we are very encouraged to see that the complementary effect of this combination has the potential to increase anti-tumor activity in patients with dMMR or MSI-H metastatic colorectal cancer,” said Ian M. Waxman, MD, development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are continuing to increase our understanding of the benefit of Immuno-Oncology based combinations and look forward to further evaluating the potential of our immunotherapy treatments in colorectal cancer patients.”

Related Coverage: FDA Approves Immuno-Oncology Combination for Metastatic Colorectal Cancer