Nivolumab, Ipilimumab Combo Yields Clinically Meaningful Responses in Advanced Hepatocellular Carcinoma

Nivolumab (Opdivo) monotherapy is currently indicated for the treatment of patients with hepatocellular carcinoma who were previously treated with the targeted therapy sorafenib, sold as Nexavar, based on the CheckMate 040 trial. Assessing the safety and efficacy of nivolumab in combination with ipilimumab (Yervoy) among these patients, researchers have observed clinically meaningful responses and an acceptable safety profile.

Presented at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, these findings showed an overall response rate (ORR) associated with the combination that was double that seen with nivolumab therapy alone. During the CheckMate 040 trial, nivolumab monotherapy yielded an ORR of 14%. These new data on the treatment combination showed an ORR of 31%.

Seven patients achieved a complete response with a median duration of response of 17 months. There was a disease control rate of 49%.

According to the researchers, this is the first report of efficacy and safety of the combination in the patient population.

With a cutoff date of September 25, 2018, the researchers observed a total of 148 patients randomized to 3 treatment groups:

• Group A: Four doses of Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks
• Group B: Four doses of Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks, each followed by nivolumab 240 mg one every 2 weeks
• Group C: Nivolumab 3 mg/kg every once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks.

Patients were treated until disease progression or intolerable toxicity. At the end of 24 months of follow-up, there was an OS rate of 40%.

Patients in Group A demonstrated the greatest response, with a median OS of 23 months. At 12 months, OS was 61% and at 24 months, OS was 48%. Sixteen (32%) of the 50 patients achieved any response, with 4 experiencing a complete response and 12 experiencing a partial response. Nine patients experienced stable disease and 20 experienced disease progression.

In Group B, there was a median OS of 12 months among the 49 patients. At 12 months, OS was 56% and at 24 months, OS was 30%. Fifteen patients achieved any response, with 3 experiencing a complete response and 12 experiencing a partial response. Five patients had stable disease and 24 experienced disease progression.

Median OS among the 49 patients in Group C was 13 months, with a 12-month survival rate of 51% and a 24-month survival rate of 42%. No patients achieved a complete response and 15 patients achieved a partial response, while 9 experienced stable disease and 21 experienced disease progression.

Overall, the treatment combination was well tolerated, with 37% of all patients experiencing a grade 3 or 4 treatment-related adverse event. The most common adverse event was pruritus and rash, and 5% of patients had a treatment-related adverse event that led to treatment discontinuation.

Reference:

Yao T, Kang YK, Kim TU, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040. Presented at: Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract: 4012.