FDA Approves Tremelimumab, Durvalumab Combination for Unresectable Liver Cancer

The approval includes a novel dose and schedule of the combination, with a single dose of both drugs followed by durvalumab every 4 weeks in patients with unresectable hepatocellular carcinoma.

Officials with the FDA have approved a combination of tremelimumab (Imjudo, AstraZeneca) and durvalumab (Imfinzi, AstraZeneca) for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide, according to an AstraZeneca press release. It is the fastest rising cause of cancer-related deaths in the United States, with approximately 36,000 new diagnoses each year.

“In the past, patients living with liver cancer had few treatment options and faced poor prognoses,” said Andrea Wilson Woods, president and founder of Blue Faery: The Adrienne Wilson Liver Cancer Foundation, in the press release. “With this approval, we are grateful and optimistic for new, innovative, therapeutic options. These new treatments can improve long-term survival for those living with unresectable hepatocellular carcinoma, the most common form of liver cancer.”

The approval includes a novel dose and schedule of the combination, with a single dose of the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody tremelimumab 300 mg in addition to the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab 1500 mg, followed by durvalumab every 4 weeks. This regimen is called the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen.

The approval is based on positive results from the HIMALAYA phase 3 trial. In this trial, patients treated with the combination experienced a 22% reduction in the risk of death versus patients treated with sorafenib. The study also showed that an estimated 31% of patients treated with the combination were still alive after 3 years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” said Ghassan Abou-Alfa, MD, MBA, principal investigator in the HIMALAYA phase 3 trial, in the press release. “In addition to this regimen demonstrating a favorable 3-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.”

The trial included 1324 participants with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy. It was conducted in 181 centers across 16 countries, with a primary endpoint of overall survival (OS). Key secondary endpoints included OS for durvalumab versus sorafenib, objective response rate, and progression-free survival for the combination and for durvalumab alone.

Durvalumab is a human monoclonal antibody that binds to the PD-L1 protein and blocks its interaction with the programmed cell death protein 1 (PD-1) and CD80 proteins. It was recently approved to treat patients with advanced biliary tract cancer in the United States based on results from the TOPAZ-1 phase 3 trial and it is the only approved immunotherapy in the curative-intent setting of unresectable, stage 3 non-small cell lung cancer for patients whose disease has not progressed after chemoradiotherapy.

Tremelimumab is a human monoclonal antibody targeting CTLA-4. It blocks the activity of CTLA-4, contributing to T-cell activation. In addition to the HIMALAYA trial, it is being tested in combination with durvalumab across multiple tumor types, including locoregional HCC, small cell lung cancer, and bladder cancer.

“With this first regulatory approval for Imjudo, patients with unresectable liver cancer in the United States 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,” said Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, in the press release.

REFERENCE

Imjudo (tremelimumab) in combination with Imfinzi (durvalumab) approved in the US for patients with unresectable liver cancer. News release. AstraZeneca; October 24, 2022. Accessed October 24, 2022. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2022/imjudo-tremelimumab-in-combination-with-imfinzi-durvalumab-approved-in-the-us-for-patients-with-unresectable-liver-cancer.html