The FDA approved the combination use of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (Nexavar), according to Bristol Myers Squibb (BMS).
The agency approved a dose of 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab under accelerated approval, the only dual immunotherapy approved by the FDA in this setting.
“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,” Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb, said in a press release. “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.”
The approval was based on overall response rate (ORR) and duration of response (DOR) seen in the phase I/II CheckMate-040 trial’s cohort treated with the combination.
After a minimum follow up of 28 months in the trial, 16 of 49 patients (33%) treated with nivolumab in combination with ipilimumab responded to treatment (95% CI, 20-48). Of this group, four (8%) experienced a complete response (CR) and 12 (24%) had a partial response (PR).
DOR ranged from 4.6-30.5-plus months, with 88% lasting at least 6 months, 56% at least 12 months, and 31% at least 24 months.
ORR assessed by Blinded Independent Central Review (BICR) using modified RECIST was 35% (95% CI, 22-50), with a CR reported in 12% of patients and a PR reported in 22%.
Serious adverse events (AEs) occurred in 59% of patients receiving the combination, and treatment was discontinued in 29% of patients and delayed in 65% of patients for an AE.
Serious AEs included pyrexia, diarrhea, anemia, increased aspartate aminotransferase, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. The most common AEs were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and decreased weight (20%).
“HCC is an aggressive disease in need of different treatment approaches,” Anthony B. El-Khoueiry, MD, 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, said in the release. “The overall response rate observed in the Opdivo (plus) Yervoy cohort of the CheckMate-040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients.”
Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials, according to the BMS release.
Bristol Myers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) for Patients with Hepatocellular Carcinoma (HCC) Previously Treated with Sorafenib. Available from: https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-opdivo-nivolumab-ye-0. Accessed Mawrch 11, 2020.