Nivolumab Indication Added for MSI-H or dMMR Metastatic Colorectal Cancer

FDA’s accelerated approval based on tumor response rates and duration of response

The FDA has approved a ninth indication for Bristol-Myers Squibb’s Opdivo (nivolumab injection for intravenous use). The new indication allows the treatment of adult and pediatric patients 12 years of age and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. This indication was granted accelerated approval based on patients’ overall response rate (ORR) and duration of response in the CheckMate-142 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CheckMate-142, a phase 2, multicenter, open-label, single-arm study, is evaluating nivolumab in patients with locally determined dMMR or MSI-H mCRC whose disease had progressed during, after, or were intolerant to, prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. In this study, 74 patients received nivolumab 3 mg/kg administered intravenously every two weeks. (The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.) Across the 74 patients, 72% received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Efficacy outcome measures included independent radiographic review, committee-assessed confirmed ORR (per RECIST 1.1 criteria) and duration of response. More than half of the patients (51%) had a BRAF (16%) or KRAS (35%) mutation.

Nivolumab demonstrated an ORR of 28% in patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, including a 1.9% complete response rate and a 26% partial response rate. Median duration of response in these patients was not reached. Among all enrolled patients, 32% responded to treatment with nivolumab, including a 2.7% complete response rate and a 30% partial response rate. The median duration of response was not reached.

“As the third most common type of cancer in the United States, our view is that colorectal cancer—particularly for those with dMMR or MSI-H metastatic disease—has been in need of new research and treatments. The approval of Opdivo for appropriate patients with this disease gives the community more hope,” said Michael Sapienza, chief executive officer of the Colon Cancer Alliance.

The most common adverse reactions occurring at an incidence of 20% or greater in patients who received nivolumab as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia.

Source: Bristol-Myers Squibb; August 1, 2017.