On October 15, Hengrui Medicine issued an announcement announcing that it had received a "confirmation letter" from the FDA, and the resubmitted PD-1 monoclonal antibody carrelizumab injection combined with apatinib mesylate tablets for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma The biologics license application (hereinafter referred to as "BLA") was accepted by the FDA. According to the Prescription Drug User Fee Act (PDUFA), the FDA's target review date for carrelizumab injection is March 23, 2025.

In October 2023, Hengrui Medicine reached a licensing agreement with Elevar Therapeutics, granting the latter exclusive rights to develop and commercialize carrelizumab liver cancer combination therapy worldwide, excluding Greater China and South Korea. In May this year, HLB-LS, the parent company of Elevar Therapeutics, announced that it had received a complete response letter (CRL) from the FDA regarding the new drug application (NDA) for carrelizumab combined with apatinib for the first-line treatment of patients with unresectable hepatocellular carcinoma. The FDA mainly emphasized two items in the CRL: ① Chemistry, manufacturing and control (CMC) issues; ② FDA's inspections of key clinical trial centers in Russia and Ukraine have not been completed. The chairman of HLB-LS said at the time that these problems were not fundamental problems and would work with Hengrui Medicine as soon as possible to resolve FDA's concerns and submit relevant documents in a timely manner. In December 2018, the international multicenter Phase III clinical trial of carrelizumab injection combined with apatinib mesylate tablets for the first-line treatment of hepatocellular carcinoma (study number: SHR-1210-Ⅲ-310) was approved for conduct in the United States.

In the second quarter of 2022, the independent data monitoring committee (IDMC) of the SHR-1210-Ⅲ-310 study determined that the results of the primary study endpoints met the pre-set superiority criteria of the protocol. The results showed that carrelizumab combined with apatinib compared with sorafenib as first-line treatment can significantly prolong the progression-free survival (PFS) and overall survival (OS) of patients with advanced hepatocellular carcinoma. SHR-1210-Ⅲ-310 is a randomized, controlled, open, international multicenter Phase III clinical study to evaluate the efficacy and safety of carrelizumab combined with apatinib compared with sorafenib in the treatment of patients with unresectable or metastatic hepatocellular carcinoma who have not received systemic treatment before. Professor Qin Shukui of the Cancer Center of Nanjing Jinling Hospital served as the global principal investigator, and 95 centers in 13 countries and regions around the world participated.

A total of 543 subjects were enrolled in this study, and they were randomly assigned in a 1:1 ratio to receive carrelizumab (200 mg, injected once every 2 weeks) combined with apatinib (250 mg, taken orally once a day) or sorafenib (400 mg, taken orally twice a day). The results showed that carrelizumab combined with apatinib as a first-line treatment for advanced hepatocellular carcinoma had significant survival benefits and tolerable safety, with a median progression-free survival (PFS) of 5.6 months and a median overall survival (OS) of 22.1 months, which is the longest OS benefit combination for first-line treatment of advanced hepatocellular carcinoma. This is the first and currently the only successful Phase III trial of immunotherapy combined with small molecule tyrosine kinase inhibitors for the treatment of advanced hepatocellular carcinoma. In June 2024, at the annual meeting of the American Society of Clinical Oncology (ASCO), the final survival analysis results of a clinical study of carrelizumab combined with apatinib versus sorafenib as first-line treatment for advanced liver cancer were announced. The results showed that compared with standard treatment, the median overall survival (OS) of the carrelizumab combined with apatinib group was significantly prolonged to 23.8 months, setting a new record for patient survival benefits.

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