Study of a Tremelimumab-Imfinzi Combination May Lead to New Liver Cancer Treatment Strategy

New major trial results reported by AstraZeneca using an investigational drug combination may result in an approval of a new regiment for liver cancer treatment.

In the HIMALAYA phase 3 trial presented recently at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, a single priming dose of tremelimumab plus Imfinzi (durvalumab) resulted in a significant and clinically meaningful improvement in overall survival (OS) compared with Bayer’s Nexavar (sorafenib) as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC), AstraZeneca said in a news release. The patients had not received prior systemic therapy and were not eligible for localized treatment.

The combination of the two drugs every four weeks reduced risk of death by 22%. Compared with Nexavar, the two drugs showed no increase in severe liver toxicity and fewer discontinuations due to treatment-related adverse events, according to AstraZeneca.

The study marks the first time an anticytotoxic T lymphocyte-associated antigen (anti-CTLA4) antibody such as tremelimumab has been dosed in this novel way in a phase 3 trial, Sunil Verma, senior vice president, Global Head of Oncology, Medical for AstraZeneca, said in an interview Managed Healthcare Executive®.

The single, high priming dose is designed to boost the patient’s own immune system against their liver cancer, aiming to maximize efficacy and minimize side effects.

“The HIMALAYA trial reinforces our scientific approach of adding tremelimumab to Imfinzi, tapping into the potential of CTLA-4 inhibition and a unique dosing regimen to prime the immune system, to help patients live longer and with manageable side effects,” Verma said.

New types of treatment are needed for liver cancer and HCC, the third-leading

cause of cancer death and the sixth most commonly diagnosed cancer worldwide, according to AstraZeneca. Company officials are

Approximately 80,000 people in the U.S., Europe and Japan are diagnosed with advanced, unresectable HCC each year and more than three times that many (260,000 people) are diagnosed in China. Only 7% of patients with advanced disease survive five years. HCC is the most common type of liver cancer, accounting for about 90% of cases. Infections with the hepatitis B or hepatitis C virus is among the most common risk factors.

Nexavar is a tyrosine kinase inhibitor, which works by disrupting the signal transduction pathways of protein kinases by several modes of inhibition.

Nexavar has proven to be effective as a monotherapy. Results from the placebo-controlled SHARP study showed that it was safe and effective as a first-line therapy of HCC patients with well-preserved liver function that were not eligible for surgical or locoregional therapies, according toFuture Medicine.

The drug was associated with a significantly increased median survival of 10.7 months compared with 7.9 months in patients receiving placebo, and progression-free survival was significantly longer.