HONG KONG, November 23 2023 -- Akeso (9926. HK) has announced that the AK104-303 Phase III trial, which investigated cadonilimab (Akeso’s PD-1/CTLA-4 bispecific antibody) combined with platinum-based chemotherapy +/- bevacizumab, has met one of its primary endpoints of progression-free survival (PFS) for first-line treatment of recurrent/metastatic cervical cancer (R/M CC), with p-value of less than 0.0001.
The AK104-303 trial represents a significant milestone as the first Phase III clinical trial investigating the combination of a PD-1/CTLA-4 bispecific antibody with platinum-based chemotherapy +/- bevacizumab for first-line treatment of recurrent/metastatic R/M CC. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS) assessed by blinded independent central review (BICR) based on RECIST v1.1 criteria. In the study, approximately 26% of patients had tumors with PD-L1 CPS < 1. Public data indicates that approximately 11% of patients in the KEYNOTE-826 study had PD-L1 CPS < 1.
During a pre-specified interim analysis conducted by an independent data monitoring committee (IDMC) in the intent-to-treat (ITT) population, cadonilimab combined with platinum-based chemotherapy +/- bevacizumab demonstrated a statistically significant and clinically meaningful PFS benefit compared to placebo combined with platinum-based chemotherapy +/- bevacizumab in all-comer patients, irrespective of their PD-L1 status, including both the PD-L1 CPS ≥ 1 and PD-L1 CPS < 1 populations.
A trend in improvement in overall survival (OS), which is the other primary endpoint, was observed for cadonilimab combination versus placebo in combination with platinum-based chemotherapy +/- bevacizumab. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.
The safety profile of cadonilimab remains consistent with previous clinical results with no new safety signals identified.
The successful achievement of the primary endpoint of PFS in the Phase III trial of cadonilimab for first-line cervical cancer is yet another milestone for the drug in first-line therapy, following the earlier achievement of the primary endpoint in first-line gastric cancer and the planned sNDA by Akeso.
In Jun 2022, cadonilimab was approved for second/third line treatment of advanced cervical cancer. With the encouraging outcomes observed in cadonilimab’s registration trials across diverse indications, especially in first-line therapies, the potential patient population eligible for cadonilimab is anticipated to expand rapidly. This expansion will effectively harness the clinical value of this novel bispecific immuno-oncology therapy, bringing benefits to a larger number of patients.
“We are delighted to once again witness the remarkable improvement in progression-free survival achieved with cadonilimab in first-line treatment of all-comer patients with advanced cervical cancer,” said Dr. Yu Xia, Founder, Chairwoman, President, and CEO of Akeso. “This outcome not only reaffirms the advantages of cadonilimab observed in the Phase II trials of cervical cancer and other trials, particularly in gastric cancer, but also further validates its exceptional clinical value in cancer treatment. We extend our heartfelt appreciation to all the researchers, participants, and patients who contributed to this trial. It is thanks to your efforts and dedication that a broader population of cervical cancer patients in China will have the opportunity to undergo a novel bispecific IO therapy, thereby enhancing treatment effectiveness and improving survival rates.”
