FDA Approves Nivolumab Plus Ipilimumab for Advanced HCC

The Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the treatment of patients with advanced hepatocellular carcinoma (HCC), who were previously treated with sorafenib (Nexavar), according to Bristol Myers Squibb, the manufacturer of the immunotherapy agents.

“HCC is an aggressive disease in need of different treatment approaches,” said Anthony B. El-Khoueiry, M.D., lead investigator and associate professor of clinical medicine and phase I program director at the Keck School of Medicine, University of Southern California (USC) and the USC Norris Comprehensive Cancer Center, in a press release.

“The overall response rate observed in the Opdivo + Yervoy cohort of the CheckMate -040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients.”

The approval was based off findings from the phase I/II, open-label, multi-cohort CheckMate-040 trial (NCT01658878), which was presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting. The trial investigated the immunotherapy combination for patients with or without chronic hepatitis who had advanced HCC and were naïve, intolerant to, or progressed on previous treatment with sorafenib.

Primary endpoints of CheckMate-040 were safety and tolerability, as well as objective response rate (ORR) based on investigator assessment with RECIST v1.1. At a minimum follow-up of 28 months, there was a 33% response rate, with 8% of patients having a complete response.

ORR was 35%, and complete response (CR) was 12%. 22% of patients had partial responses.

Secondary endpoints of the trial were disease control rate, duration of response, overall survival, time to response, time to progression, and progression-free survival (PFS). Duration of responses ranged from 4.6 to over 30.5 months, and the majority of responses (88%) lasted at least 6 months. More than half (56%) lasted 12 months or longer, and 31% lasted at least 24 months.

“The incidence of liver cancer is rising in the United States, and HCC is the most common and aggressive form of the disease,” said Andrea Wilson, president and founder, Blue Faery: The Adrienne Wilson Liver Cancer Association, in a statement. “Today’s approval provides a new option for patients with HCC previously treated with sorafenib, giving the community more hope.”

A total of 59% of patients given the immunotherapy combination had serious adverse events (AEs), with 29% discontinuing treatment and 65% delating treatment. Serious AEs reported in at least 4% of patients included: pyrexia, diarrhea, anemia, increase AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.

Common AEs (occurring in more than 20% of patients) included: rash, pruiritus, musculoskeletal pain, cough, decreased appetite, fatigue, pyrexia, abdominal pain, nausea, dizziness, hypothyroidism, and decreased weight.

“We recognize there is a critical need to provide patients with aggressive forms of cancer, like HCC, new treatment options that may offer clinically meaningful and ultimately durable responses,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. “Today’s announcement builds on our legacy in pioneering immunotherapy treatments and is an important step in our commitment to transforming patients’ lives through science.”