Bristol-Myers Squibb announced that the Food and Drug Administration (FDA) has approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib. 

The approval is supported by data from the open-label, phase 1/2 CheckMate -040 study that included a cohort of patients (N=49) with HCC who progressed on or were intolerant to sorafenib, and received Opdivo 1mg/kg intravenously (IV) plus Yervoy 3mg/kg IV every 3 weeks for 4 doses, followed by Opdivo 240mg every 2 weeks until disease progression or unacceptable toxicity. The primary end point was confirmed overall response rate (ORR), assessed by Blinded Independent Central Review (BICR) using RECIST v1.1 and modified RECIST (mRECIST); duration of response (DOR) was also assessed.

After a minimum follow up of 28 months, results showed an ORR of 33% (n=16; 95% CI, 20-48), a complete response of 8% (n=4) and a partial response of 24% (n=12) in the Opdivo plus Yervoy cohort. Patients demonstrated a DOR ranging from 4.6 to 30.5+ months; DOR ≥6 months, ≥12 months, and ≥24 months were observed in 88%, 56%, and 31% of patients, respectively. Objective response rate and DOR were assessed using RECIST v1.1. When assessed using mRECIST, ORR was 35% (n=17; 95% CI, 22-50), with complete response reported in 12% of patients (n=6) and partial response in 22% (n=11). 

With regard to safety, the most common adverse reactions observed 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%). Treatment was discontinued in 29% of patients and delayed in 65% due to an adverse reaction.

The FDA granted accelerated approval for this indication based on ORR and DOR observed in the Opdivo plus Yervoy cohort; continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

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Opdivo plus Yervoy is already indicated for the treatment of unresectable or metastatic melanoma; for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC); and for the treatment of microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).

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