FDA Approves Nivolumab plus Ipilimumab for Treatment of Hepatocellular Carcinoma

The US Food and Drug Administration (FDA) has approved nivolumab and ipilimumab (Opdivo + Yervoy) combination for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, according to a statement from Bristol Myers Squibb.

The approval for HCC is based on the results of the phase 1/2 CheckMate-040 trial, which indicated 33% of patients responded to the dual immunotherapy, and marks the fourth type of cancer nivolumab and ipilimumab has received approval for treating.

“HCC is an aggressive disease in need of different treatment approaches,” said Anthony 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, in a statement. “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.”

As the most common form of liver cancer, the need for effective therapies for the treatment of HCC is critical—indicated by the accelerated approval given to nivolumab and ipilimumab. The phase 1/2 CheckMate-040 trial indicated 33% of HCC patients previously treated with sorafenib saw at least a partial response at 28 months and 4% had a complete response, according to Bristol Myers Squibb.

Furthermore, results of the trial indicated that 88% of patients who had a response had a response that lasted 6 months or more and 31% had a response for 24 months or more. The statement from Bristol Myers Squibb noted the newest indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Multiple adverse events for were reported during CheckMate-040 study—treatment was discontinued in 29% and delayed in 65% due to an adverse reaction. Adverse events common in the study 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 decreases in weight (20%). Serious adverse events—defined as reported in 4% of patients or more—were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.

With the approval for HCC, nivolumab and ipilimumab have received approval for treatment in patients with unresectable or metastatic melanoma, intermediate or poor risk, previously untreated advanced RCC, adults and pediatric patients 12 years and older with MSI-H or dMMR metastatic CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

“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, US, Oncology, Immunology, Cardiovascular with Bristol Myers Squibb, in a statement. “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.”