FDA Approves Immuno-Oncology Combination for Metastatic Colorectal Cancer

The FDA has approved nivolumab (Opdivo) 3 mg/kg in combination with low-dose ipilimumab (Yervoy) 1 mg/kg (injections for intravenous use) for the treatment of metastatic colorectal cancer, according to a press release.

The newly approved indication includes the treatment of adult and pediatric patients 12 years and older with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

According to the press release, approximately 5% of metastatic CRC patients have dMMR or MSI-H tumors. These patients are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

The accelerated approval is based on overall response rate and duration of response (DOR), and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials, according to Bristol-Myers Squibb.

In the ongoing phase 2 CheckMate-142 study evaluating the combination therapy, 46% of the 82 patients who had received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan responded to treatment with nivolumab plus ipilimumab. Among those who responded to the treatment, the median DOR was not reached. Eighty-nine percent of those patients had responses of 6 months or longer and 21% had responses of 12 months or longer.

Related Coverage: Variations and Nuances in Colorectal Cancer Drug Dosing

Among all 119 patients enrolled, 49% responded to treatment with nivolumab plus ipilimumab, and 4.2% experienced a complete response, while 45% experienced a partial response. Among those who responded to treatment overall, the median DOR was not reached. Eighty-three percent of those patients had responses of 6 months or longer and 19% had responses of 12 months or longer.

“Metastatic colorectal cancers with dMMR or MSI-H biomarkers can be difficult to treat and some patients may need additional options,” Heinz-Josef Lenz, MD, FACP, principal investigator of the study, said in a press release. “The FDA’s approval of an I-O/I-O combination provides with us an encouraging approach to address this challenging disease in patients who have progressed following treatment with 3 standard chemotherapy options.”

In the nivolumab plus ipilimumab cohort of the trial, 86% of patients received all 4 doses of the combination treatment. Nivolumab was discontinued in 13% of patients and delayed in 45% of patients due to an adverse reaction.

The nivolumab plus ipilimumab combination is also approved to treat patients with intermediate- or poor-risk renal cell carcinoma and patients with unresectable or metastatic melanoma.

Reference

Bristol-Myers Squibb’s Opdivo^® (nivolumab) + Low-Dose Yervoy ^® (ipilimumab) is the First Immuno-Oncology Combination Approved for MSI-H/dMMR mCRC Patients Who Progressed Following Treatment with a Fluoropyrimidine, Oxaliplatin and Irinotecan [news release]. Bristol-Myers Squibb’s website. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibbs-opdivo-nivolumab-low-dose-yervoy-ipilimu. Accessed July 11, 2018.