Updated results from the Phase III HIMALAYA trial reveal that AstraZeneca's Imfinzi (durvalumab) combined with Imjudo (tremelimumab) provides a sustained and clinically meaningful overall survival (OS) benefit at five years for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were ineligible for localized treatment. The findings, presented at the European Society for Medical Oncology (ESMO) Congress 2024, mark the longest survival follow-up reported for a Phase III immunotherapy trial in this setting.
At a five-year follow-up, the exploratory analysis showed that the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab), which includes a single priming dose of Imjudo added to Imfinzi, reduced the risk of death by 24% compared to sorafenib (HR=0.76; 95% CI: 0.65-0.89). An estimated 19.6% of patients treated with the STRIDE regimen were alive at five years, versus 9.4% of those treated with sorafenib.
In a subgroup analysis of patients who achieved disease control (complete or partial response, or stable disease), 28.7% of those treated with the STRIDE regimen were alive at five years, compared to 12.7% of patients treated with sorafenib. Exploratory analysis of depth of response (DpR) indicated that more patients treated with the STRIDE regimen experienced deep responses, leading to longer survival compared to sorafenib.
Expert Commentary
Lorenza Rimassa, MD, Associate Professor of Medical Oncology, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, and a lead investigator in the HIMALAYA trial, noted, "Treatment with durvalumab plus tremelimumab for patients with advanced liver cancer doubled the overall survival rate at five years, a significant survival advantage over sorafenib that has also become even more pronounced over time. These data reinforce the use of this novel dual immunotherapy regimen and are an important milestone for patients with this devastating disease."
Safety Profile
The safety profile of the STRIDE regimen remained consistent with the known profiles of each medicine. Serious treatment-related adverse events (Grade 3 or 4, including death) were experienced by 17.5% of patients treated with the STRIDE regimen versus 9.9% of patients treated with sorafenib, with no new events occurring after the primary analysis for STRIDE.
Regulatory Status and Disease Context
Imfinzi in combination with Imjudo is approved for the treatment of adults with advanced or unresectable HCC in the US, EU, Japan, and several other countries. Liver cancer, primarily HCC, is the third-leading cause of cancer death, with approximately 900,000 people diagnosed each year globally. The five-year survival rate for advanced-stage HCC is only 7%.
Trial Design
HIMALAYA is a randomized, open-label, multi-center, global Phase III trial involving 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy. The primary endpoint was OS for the combination versus sorafenib, with key secondary endpoints including OS for Imfinzi versus sorafenib, objective response rate, and progression-free survival (PFS) for the combination and for Imfinzi alone.
About Imfinzi and Imjudo
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein, blocking its interaction with PD-1 and CD80 proteins, thereby countering the tumor's immune-evading tactics. Imjudo (tremelimumab) is a human monoclonal antibody that targets CTLA-4, contributing to T-cell activation and priming the immune response to cancer.
