FDA Approves Durvalumab/Tremelimumab in Unresectable HCC

FDA

The FDA has approved durvalumab (Imfinzi) in combination with tremelimumab (Imjudo) for the treatment of adult patients with unresectable hepatocellular carcinoma.¹

The approval is based on findings from the phase 3 HIMALAYA trial (NCT03298451), in which the combination of durvalumab/tremelimumab led to a 22% reduction in the risk of death vs sorafenib (Nexavar; HR, 0.78; 95% CI, 0.66-0.92; P = .0035).²

In data published in the New England Journal of Medicine Evidence, approximately 31% of patients treated with the combination were still alive after 3 years vs 20% of patients on sorafenib.³

The combination is administered via the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen, which comprises a single dose of tremelimumab at 300 mg plus durvalumab at 1500 mg, followed by durvalumab every 4 weeks.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival. In addition to this regimen demonstrating a favourable three-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease," lead study investigator Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center (MSK), stated in a news release.

In the open-label, multicenter, international phase 3 HIMALAYA study, investigators evaluated single-agent durvalumab at 1500 mg alone (n = 389), durvalumab with a single priming dose of tremelimumab at 300 mg every 4 weeks (n = 393), or sorafenib (n = 389) patients with unresectable advanced HCC. Patients had not been treated with a prior systemic treatment and were ineligible for locoregional therapy.

HIMALAYA was conducted in 181 centres across 16 countries, which included the United States, Canada, Europe, South America and Asia.

Overall survival (OS) was the primary end point for the combination vs sorafenib; key secondary end points included OS for durvalumab vs sorafenib, and objective response rate and progression-free survival (PFS) for the combination and for the checkpoint inhibitor alone.

In the New England Journal of Medicine data, the median OS was 16.43 months (95% CI, 14.16-19.58) with the combination and 16.56 months (95% CI, 14.06- 19.12) with durvalumab alone, and 13.77 months (95% CI, 12.25-16.13) with sorafenib. The 3-year OS rates were 30.7%, 24.7%, and 20.2%, respectively.

The OS hazard ratio for the combination vs sorafenib was 0.78 (96.02% CI, 0.65-0.93; P = .0035). With single-agent durvalumab, the OS hazard ratio was noninferior to sorafenib (HR, 0.86; 95.67% CI, 0.73-1.03; noninferiority margin, 1.08).

The median PFS was not significantly different between the 3 arms.

Regarding safety, the profiles were found to be consistent with each agent alone, and no new safety signals were identified. Grade 3/4 treatment-emergent adverse events occurred in 50.5% of patients with the combination, 37.1% with durvalumab, and 52.4% with sorafenib.

The regulatory applications for the immunotherapy combination are under review in Europe, Japan, and other countries for the treatment of patients with advanced liver cancer, also based on the HIMALAYA data.

“With this first regulatory approval for Imjudo, patients with unresectable liver cancer in the US now have an approved dual immunotherapy treatment regimen that harnesses the potential of CTLA-4 inhibition in a unique combination with a PD-L1 inhibitor to enhance the immune response against their cancer,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, the developer of the agents, said in the news release.

References

1. Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News release. AstraZeneca. October 24, 2022. Accessed October 24, 2022. https://bit.ly/3VUsQTw
2. Imfinzi and Imjudo US prescribing information. 2022.
3. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. N Eng J Evid. 2022;1(8). doi: 10.1056/EVIDoa2100070