Final analysis of the Himalaya trial demonstrated safety as well as a statistically relevant 22% improvement of overall survival (OS) without exposing the patient to an increase in liver toxicity.
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AstraZeneca has filed a Biologics Licensing Application (BLA) with the U.S. Food and Drug Administration for tremelimumab, hoping to expand treatment options for patients diagnosed with unresectable hepatocellular carcinoma (HCC).
The application has been granted Priority Review status, shortening the expected review timeline to six months, according to guidelines published by the administration. Tremelimumab is an anti-cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4) antibody that upregulates T-cell activation and immune response to cancer.
Multiple clinical trials have been conducted to determine the safety and efficacy of tremelimumab in combination with Imfinzi (durvalumab), in support of the BLA. The latter is a monoclonal antibody formulation designed to target cancer cells by manipulating programmed death ligand 1 protein (PD-L1) signaling. By blocking PD-P1 signaling, the cancer cells are revealed to the immune system, rather than being cloaked by the immune checkpoint. Indications could span multiple cancers, including blood, bladder, pancreatic, gastric, head and neck and non-small cell lung cancer, following an accumulation of enough supportive data to file additional BLAs.
The application was filed after analysis of data from the open-label Phase III Himalaya trial. The study focused on treating 1,324 patients diagnosed with HCC who had not been given systemic therapies such as immunotherapy and were determined to be ineligible for localized treatments such as surgery or radiation. Final analysis of the trial demonstrated safety as well as a statistically relevant 22% improvement of overall survival (OS) without exposing the patient to an increase in liver toxicity.
A supplemental BLA (sBLA) has been filed for Imfinzi. Following the announcement of the two applications, AstraZeneca’s vice president of oncology research and development, Susan Galbraith said “The HIMALAYA Phase III trial showed an unprecedented three-year overall survival in this setting with a single priming dose of tremelimumab added to Imfinzi, highlighting the potential for this regimen to improve longer-term survival outcomes. Patients with advanced liver cancer are in great need of new treatment options, and we are working closely with the FDA to bring this novel approach to patients in the U.S. as soon as possible.”
The initial combination dose serves as a primer dose, which is believed to improve the efficacy and safety of the subsequent doses. In 2020, Orphan Drug Designations were granted for Imfinzi and tremelimumab by the FDA. An additional Orphan Designation was given for tremelimumab by the European Union.
The statistics associated with an advanced case of HCC are devastating, as a mere 3% of patients survive five years. This percentage is given additional weight by the fact that HCC is the most common form of liver cancer, topping cancer death charts as the sixth most prevalent.
