On October 21, the FDA’s official website showed that AstraZeneca’s anti-CTLA-4 monoclonal antibody tremelimumab (temslimumab) was approved by the FDA for listing, and the approved indication was a single starting dose of tremelimumab in combination with durvalumab. Unresectable hepatocellular carcinoma with first-line therapy. The combination regimen is called STRIDE (single tremelimumab regular interval durvalumab).
Liver cancer is the third leading cause of cancer death worldwide (after lung cancer and colorectal cancer) and the sixth most common cancer worldwide. Among them, hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 75% to 85%. There are approximately 26,000 patients with advanced, unresectable HCC each year in the United States.
Tremelimumab is a humanized monoclonal antibody developed by Pfizer that promotes cancer cell death by blocking the activity of CTLA-4 on the surface of T lymphocytes, helping to activate T cells and enhance the immune response to tumors. In October 2011, MedImmune (a subsidiary of AstraZeneca) reached an agreement with Pfizer to acquire the global development rights of tremelimumab, while Pfizer retained the rights to develop certain specific combination therapies. In January 2020, the STRIDE program was granted orphan drug designation by the FDA for the treatment of HCC.
The FDA approval is based on the results of a Phase III HIMALAYA study. This study is a global, multicenter, randomized, open-label clinical trial involving 1324 patients to evaluate the efficacy and safety of STRIDE regimen versus valliumab monotherapy and sorafenib monotherapy in patients with unresectable HCC. safety. These patients had not received prior systemic therapy and were not eligible for topical therapy. The primary endpoint of the trial is overall survival (OS), and secondary endpoints include time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). .
The results showed that compared with the sorafenib group, patients in the STRIDE regimen group had a 22% lower risk of death (HR: 0.78; 96.02% CI: 0.65-0.93; P=0.0035). In addition, 31% of patients were still alive at 3 years, compared with 20% in the sorafenib group.
In terms of safety, the safety of the STRIDE regimen and Imfinzi monotherapy was consistent with previous reports, and no new safety signals were found.
As of recently, 5 CTLA-4 mAbs have been approved for marketing in the world, namely kadunilimumab, belatacept, ipilimumab, abatacept and tremelimumab. In addition, PSB205 co-developed by Qilu Pharma and Sound Biologics, erfonrilimab co-developed by Corning & Jereh, and quavonlimab co-developed by Merck and Kangfang Biologics are undergoing Phase III clinical trials.