AstraZeneca’s Imfinzi, Tremelimumab Combo Significantly Improves Overall Survival in Phase 3 Trials

On October 15th, AstraZeneca announced encouraging results for its tremelimumab plus Imfinzi (durvalumab) antibody combination in a Phase 3 trial conducted in patients with hepatocellular carcinoma (HCC).

Results from the Phase 3 HIMALAYA trial showed that a high priming dose of tremelimumab, an anti-CTLA4 antibody, added to Imfinzi demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit versus sorafenib as a 1st-line treatment for patients with unresectable HCC who had not received prior systemic therapy and were not eligible for localized treatment.

This combination of this novel dose of tremelimumab with Imfinzi is termed the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab). The combination demonstrated a favorable safety profile, and the addition of tremelimumab to Imfinzi did not increase severe hepatic toxicity, AstraZeneca said in a statement.

Imfinzi alone demonstrated non-inferior OS to sorafenib with a numerical trend in favor of Imfinzi and an improved tolerability profile compared to sorafenib.

Most Common Type of Liver Cancer

Liver cancer is the third leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide with approximately 900,000 people diagnosed each year. Only 7% of patients with advanced disease survive five years. HCC is the most common type of liver cancer and is the second most fatal cancer globally. HCC is hard to fight due to difficulties in early detection. Current treatments are restricted to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors like Nivolumab for advanced HCC patients.

 “HIMALAYA is the first Phase 3 trial to add a novel single priming dose of an anti-CTLA4 antibody to another checkpoint inhibitor, durvalumab. This serves to boost the patient’s own immune system against their liver cancer, aiming to maximize long-term survival with minimal side effects. This is very exciting news for our patients,” said Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan Kettering Cancer Center and principal investigator of the Phase 3 trial.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “Inhibition of CTLA-4 has shown the ability to drive benefit particularly in the tail of the survival curve in several settings. This is the first time a dual immunotherapy regimen has improved overall survival as a 1st-line treatment for patients with unresectable liver cancer for whom treatment options are limited and long-term outcomes are poor.”

Author

Rajaneesh K. Gopinath