AstraZeneca PLC Sponsored ADR (AZN.US) "dual immunotherapy" new indication approved for market in China

On April 27, Astrazeneca PLC Sponsored ADR (AZN.US) announced that the National Medical Products Administration (NMPA) of China has formally approved the use of Imfinzi (durvalumab) in combination with Imjudo (tremelimumab) as first-line treatment for adult patients with advanced or unresectable hepatocellular carcinoma (HCC). In addition, durvalumab has also been approved for monotherapy as first-line treatment for adult patients with advanced or unresectable HCC. Tremelimumab is a human monoclonal antibody that was first approved by the US FDA for marketing in October 2022, in combination with durvalumab as first-line treatment for unresectable HCC adult patients, becoming the second CTLA4 antibody approved for marketing globally. It was subsequently approved for marketing in Japan, the EU in December of the same year and February of the following year. In addition to approved indications for liver cancer and lung cancer, the efficacy of tremelimumab in combination with durvalumab is being evaluated in various tumor types suitable for localized treatment, including HCC, SCLC, NSCLC, and bladder cancer. The approval for this new indication is based on the positive results from the global Phase III HIMALAYA study and the Chinese cohort. The HIMALAYA study is a randomized, open-label, global, multicenter Phase III clinical study that compared the efficacy of monotherapy with durvalumab and the combination of tremelimumab starting with a single dose of 300mg and durvalumab at 1500mg given every four weeks, with the effect of monotherapy with the standard treatment of the multikinase inhibitor sorafenib. Global cohort data shows that the STRIDE regimen can significantly reduce the risk of death by 22% compared to sorafenib monotherapy (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.66-0.92; p=0.0035). The median overall survival (OS) for patients in the STRIDE group was 16.4 months, while the sorafenib group was 13.8 months. Durvalumab monotherapy showed non-inferior OS benefit compared to sorafenib (HR 0.86; 95% CI, 0.73-1.02), with a prespecified non-inferiority boundary of 1.08 (based on the upper limit of the 95.67% CI), and a median OS of 16.6 months in the durvalumab monotherapy group. In terms of safety, both the STRIDE regimen and durvalumab monotherapy demonstrated good safety and tolerability. The incidence of grade 3 or higher treatment-related adverse events (TRAE) was 24.1% in the STRIDE group and 12.4% in the durvalumab monotherapy group, both lower than the 40.2% in the sorafenib group.