FDA Approves Nivolumab for Hepatocellular Carcinoma

• September 24, 2017
• Drugs

he FDA has granted an accelerated approval to nivolumab (Opdivo) for the treatment of patients with hepatocellular carcinoma (HCC) following prior sorafenib (Nexavar), regardless of PD-L1 status.

The approval is based on 154 patients enrolled in the phase I/II CheckMate-040 trial, in which the overall response rate (ORR) by blinded independent central review (BICR) was 18.2% per mRECIST criteria for patients who had previously been treated with sorafenib. Additionally, 3.2% of patients experienced a complete response. The ORR by RECIST 1.1 was 14.3% with nivolumab and the response duration ranged from 3.2 to 38.2+ months.

“In recent years, there has been growing interest in leveraging immuno-oncology knowledge and discoveries to add to the treatment options available for patients with advanced-stage liver cancer,” 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 of University of Southern California (USC) and the USC Norris Comprehensive Cancer Center, said in a statement. “The approval of Opdivo provides us with an encouraging approach and a new treatment option for appropriate patients with HCC following prior systemic therapy.”

In the CheckMate-040 trial, 262 patients with advanced HCC with or without hepatitis C virus (HCV) or hepatitis B virus (HBV) infection were enrolled from November 26, 2012, to August 8, 2016. There were 48 patients in the dose-escalation phase and 214 patients in the dose-expansion phase. Seventy-seven percent of patients in the dose-escalation phase and 68% of patients in the expansion phase had prior sorafenib.

In the escalation phase, patients received 0.1 to 10 mg/kg of IV nivolumab every 2 weeks. Patients in the expansion phase received nivolumab at 3 mg/kg every 2 weeks. The FDA approval was specifically for a dose of 240 mg every 2 weeks.

The median age of patients in the escalation phase was 62 years (range, 55-69), 75% of patients were male, 58% were white, and 40% had an ECOG performance status (PS) of 1. Seventy-five percent had surgical resection and 21% had received radiotherapy. In the expansion phase the median age was of patients was 64 years (range, 56-70), 80% of patients were male, 49% were white, 47% were Asian, and 36% had an ECOG PS of 1. Sixty percent of patients had surgical resection and 19% had received radiotherapy.

According to findings presented at the 2017 ASCO Annual Meeting, in the sorafenib-experienced group in the expansion phase (n = 145), the mRECIST ORR by BICR was 19%. By RECIST v1.1 there were 2 complete responses (1%), 19 partial responses (13%), and 60 patients with stable disease (41%). The disease control rate (DCR; ORR plus stable disease) was 56%.

In the sorafenib-naïve group across both the dose expansion and escalation cohorts (n = 80), the ORR by BICR was 20% by RECIST v1.1 and 24% by mRECIST. The v1.1 analysis noted 1 complete response (1%), 15 partial responses (19%), and 27 patients with stable disease (34%). Median duration of response was 17 months.