CheckMate 040: Opdivo safe, effective in advanced HCC

BOSTON — Opdivo monotherapy was safe and effective in patients with advanced hepatocellular carcinoma, irrespective of infection status, according to results of the CheckMate 040 trial presented during a Late Breaker at The Liver Meeting 2016.

“[Hepatocellular carcinoma] is a dreadful disease that is among the leading causes of cancer-related deaths worldwide. For those patients diagnosed with hepatocellular carcinoma who have reached the advanced stage of disease, there is only one single effective systemic therapy, sorafenib. For patients who progress on this therapy, we virtually have no better thing that we can do for them other than provide symptomatic care,” Bruno Sangro, MD, of Clinica Universidad de Navarra, in Pamplona, Spain, said during his presentation.

The fully human IgG4 monoclonal antibody inhibitor of the PD-1 receptor, Opdivo (nivolumab, Bristol-Myers Squibb), has been shown to provide survival benefit in multiple malignancies, including melanoma, lymphoma, lung, kidney and head and neck cancers.

For this reason, researchers sought to assess the safety, tolerability and efficacy of dose-escalation nivolumab (0.1–10 mg/kg) once every 2 weeks in patients with advanced HCC with or without chronic HCV or HBV and with or without prior Nexavar (sorafenib, Bayer) treatment. In the phase 2 expansion stage of the phase 1 dose-escalation trial, patients received 3 mg/kg once every 2 weeks.

Primary outcomes included safety and tolerability in the dose-escalation arm (n = 48) and the objective response rate in the expansion arm (n = 214). Patients were further assessed for HCV RNA and quantitative HBV surface antigen levels (qHBsAg).

Results of the interim analysis indicated most patients who discontinued nivolumab did so because of disease progression. Only one patient in the dose-escalation cohort and eight patients in the expansion cohort discontinued nivolumab due to treatment-related toxicities.

“The manageable safety profile of nivolumab was comparable to that observed for other tumor types, without any additional safety concerns. We are very happy to report that nivolumab was very well-tolerated among our cohort of patients with advanced HCC,” Sangro said.

Overall, 15% of patients achieved an objective remission of the tumor (95% CI, 12-21), with a median response duration of 17 months (95% CI, 6-24). Fifty-percent of patients had stable disease. The overall disease control rate was 68% across all subgroups.

“Tumor shrinkage was observed in patients with different etiologies, and importantly, a significant number of them were observed in the sorafenib progressors as well as in those who were sorafenib-naive. Progression on sorafenib did not prevent tumor shrinkage,” Sangro said.

Median survival was 14.1 months (95% CI, 3.15-28.58) in patients who were sorafenib-naive and 15 months (95% CI, 4.99-18.92) in patients who progressed on sorafenib. Transient decreases in HCV RNA greater than 1 were observed among those with HCV (20%), and decreases in qHBsAg great than 1 log were achieved in 5% of patients with HBV.

“These findings are quite encouraging and support continued investigation of nivolumab in patients with advanced HCC,” Sangro said. “The phase 3 trial of nivolumab, CheckMate 459, will further assess the agent in patients with advanced HCC.”

Reference:

Sangro B, et al. Abstract LB-10. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.

Disclosure: Sangro reports no relevant financial disclosures.