Opdivo ( Nivolumab ) 1 mg/kg plus Yervoy ( Ipilimumab ) 3 mg/kg ( injections for intravenous use ) was approved by the U.S. Food and Drug Administration ( FDA ) to treat hepatocellular carcinoma ( HCC ) in patients who have been previously treated with Sorafenib.
Approval for this indication has been granted under accelerated approval based on overall response rate and duration of response seen in the Opdivo plus Yervoy cohort of the phase 1/2 CheckMate -040 trial.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
In the CheckMate -040 cohort of HCC patients previously treated with Sorafenib, after a minimum follow up of 28 months, 33% ( 16/49; 95% CI: 20-48 ) of patients responded to treatment with Opdivo plus Yervoy; 8% ( 4/49 ) had a complete response ( CR ) and 24% ( 12/49 ) had a partial response ( PR ).
Duration of responses ( DOR ) ranged from 4.6 to 30.5+ months, with 88% lasting at least six months, 56% at least 12 months and 31% at least 24 months.
Overall response rate ( ORR ) and DOR were assessed by BICR ( Blinded Independent Central Review ) using RECIST v1.1.
ORR assessed by BICR using modified RECIST was 35% ( 17/49; 95% CI: 22-50 ), with a CR reported in 12% ( 6/49 ) of patients and a PR reported in 22% ( 11/49 ) of patients.
CheckMate -040 is a phase 1/2 open-label study that included a cohort of patients with HCC who progressed on or were intolerant to Sorafenib and received Nivolumab plus Ipilimumab.
The trial included patients who were PD-L1 expressors and non-expressors.
Key eligibility criteria included histologic confirmation of HCC and Child-Pugh Class A cirrhosis status. Additional eligibility criteria included those who were infected with active HCV or active HBV, or were uninfected.
Patients with active autoimmune disease, brain metastasis, a history of hepatic encephalopathy, clinically significant ascites, infection with HIV, or active co-infection with HBV and HCV or HBV and HDV were excluded.
Patients with known fibrolamellar HCC, sarcomatoid HCC, and mixed cholangiocarcinoma and HCC were also excluded.
A total of 49 patients were treated with Nivolumab 1 mg/kg IV and Ipilimumab 3 mg/kg IV every three weeks for four doses, followed by Nivolumab 240 mg every two weeks until disease progression or unacceptable toxicity.
The major efficacy outcome was ORR, as assessed by BICR using RECIST v1.1 and mRECIST.1 Duration of response was also assessed.
The safety of Opdivo 1 mg/kg and Yervoy 3 mg/kg was evaluated in 49 patients. Serious adverse reactions occurred in 59% of patients receiving Opdivo plus Yervoy.
Treatment was discontinued in 29% of patients and delayed in 65% of patients for an adverse reaction.
Serious adverse reactions reported in greater than or equal to 4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.
The most common adverse reactions ( reported in greater than or equal to 20% of patients ) 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 weight decreased ( 20% ). ( Xagena )
Source: BMS, 2020