HONG KONG, March 14, 2023 /PRNewswire/ -- Akeso, Inc. (9926.HK) announced that patient enrollment has been completed for its pivotal Phase III clinical trial for cadonilimab (PD-1/CTLA-4 bi-specific antibody, AK104), the world's first approved and marketed dual-immune checkpoint bi-specific antibody drug, for use in combination with chemotherapy as first-line therapy for advanced gastric or gastroesophageal junction cancer (GC/GEJC). This marks a step closer to the launch of cadonilimab for a major indication, after the indication for treatment of cervical cancer has been approved. 

This clinical trial represents the world's first clinical investigation of the bispecific PD-1/CTLA-4 bispecific antibody in combination with chemotherapy for the first-line treatment of gastric cancer. A total of 610 subjects are enrolled and the primary study endpoint is to compare the OS of AK104 in combination with a XELOX regimen versus a placebo in combination with XELOX regimen in the intent-to-treat (ITT) population. The interim analysis is expected to be conducted by the end of 2023.

Several phase III studies have been conducted internationally to demonstrate the synergistic effect of immune checkpoint inhibitors in combination with chemotherapy in the treatment of GC/GEJC. Although the combination of anti-PD-1 and anti-CTLA-4 agents has a higher response rate compared to monotherapy with PD-1, the combination of single target drugs also has higher toxicities.

Combining the speech delivered by Professor Ji Jiafu, the President of Peking Cancer Hospital, at the 2022 ASCO-GI Congress, with the results by the end of 2021, the phase II trial of cadonilimab in combination with chemotherapy in first-line treatment of gastric cancer demonstrates the long-term survival benefit and favorable safety profile in the overall population.

• When only 15% of the PD-L1 population had CPS ≥ 5, the ORR reached 68.1% and the DCR reached 92.3%. In the general population, the overall median PFS was 9.2 months and the median OS was 17.08 months, significantly superior to chemotherapy and associated PD-1 therapy.
• Cadonilimab remains remarkably effective and safe in patients with low PD-L1 expression. In PD-L1 patients with CPS ≥ 1 and CPS < 1, their median OS was 17.41 months and 14.65 months respectively.
• Compared with PD-1 mAb, no new safety signal was found in cadonilimab; which therefore suggests that it is substantially safe.

In June 2022, cadonilimab was approved by NMPA for the treatment of recurrent or metastatic cervical cancer, becoming the world's first dual-immune checkpoint inhibitor to be granted such approval. Given the positive confirmatory findings of cadonilimab in advanced gastric cancer research, it is anticipated that cadonilimab will overcome existing therapeutic barriers and optimize the treatment of advanced gastric cancer, providing patients with improved survival benefits. Going forward, Akeso will focus its resources in order to speed up the development of Phase III study, as well as make preparations for the eventual product launch.