India's drug regulatory panel has approved AstraZeneca Pharma India's protocol amendment for a pivotal Phase III clinical trial investigating the combination of durvalumab and tremelimumab as a first-line treatment for patients with advanced hepatocellular carcinoma (HCC).
The Subject Expert Committee (SEC) functioning under the Central Drug Standard Control Organisation (CDSCO) granted the approval following the company's presentation of protocol amendment version 8.0 dated June 17, 2024, for protocol number D419CC00002.
Immunotherapy Combination for Advanced Liver Cancer
The approved amendment pertains to a randomized, open-label, multi-center Phase III study evaluating the efficacy and safety of durvalumab and tremelimumab in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
Durvalumab (brand name Imfinzi) is a monoclonal antibody that blocks the interaction between programmed death-ligand 1 (PD-L1) and its receptors. By preventing this interaction, durvalumab removes an inhibitory signal, allowing T cells to recognize and attack cancer cells more effectively.
Tremelimumab (brand name Imjudo) targets a different immune checkpoint protein called CTLA-4. By blocking CTLA-4, tremelimumab enhances T-cell activation and proliferation, further strengthening the immune response against tumor cells.
The dual immunotherapy approach aims to provide synergistic effects by targeting two distinct immune checkpoint pathways simultaneously, potentially offering improved outcomes for patients with this aggressive form of liver cancer.
Significant Unmet Need in Hepatocellular Carcinoma
Hepatocellular carcinoma represents the most common type of primary liver cancer and is a leading cause of cancer-related deaths worldwide. Patients with advanced HCC face a poor prognosis, with limited treatment options available, particularly in the first-line setting.
The current standard of care for advanced HCC has evolved in recent years with the introduction of targeted therapies and immunotherapies, but outcomes remain suboptimal for many patients. The durvalumab-tremelimumab combination represents a potential advancement in treatment by harnessing the body's immune system to fight the cancer through complementary mechanisms.
Parallel Development in Gastric Cancer
In a separate but related development, the SEC also approved AstraZeneca's protocol amendment for another oncology trial. This second approval concerns protocol amendment version 2.0 dated August 20, 2024, for protocol number D9802C00001, which is investigating AZD0901 in advanced gastric cancer.
AZD0901 is an antibody-drug conjugate (ADC) being developed for advanced solid tumors, including gastric cancer and adenocarcinoma of the gastroesophageal junction that express claudin18.2 (CLDN18.2). The drug combines a monoclonal antibody targeting CLDN18.2 with monomethyl auristatin E (MMAE), a potent cytotoxic agent.
The Phase III CLARITYGASTRIC01 trial is evaluating AZD0901 monotherapy compared to investigator's choice of therapy in second- or later-line adult patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma expressing CLDN18.2.
Regulatory Pathway Forward
The SEC's approval of both protocol amendments allows AstraZeneca to proceed with the modified clinical trial protocols as presented. These regulatory milestones represent important steps in the clinical development of these investigational therapies for patients with difficult-to-treat cancers.
The decisions were made during recent SEC meetings for oncology, with the durvalumab-tremelimumab amendment approved on March 11, 2025. The committee's recommendations came after detailed deliberations on the scientific and clinical aspects of the proposed changes.
As these trials progress, they will provide valuable data on the efficacy and safety of these novel therapeutic approaches in patient populations with significant unmet medical needs.
