Akeso, Inc. (9926.HK) ("Akeso" or the "Company") announced that the first patient has been dosed in a Phase III clinical study (COMPASSION-40/AK104-313) evaluating cadonilimab, its first-in-class PD-1/CTLA-4 bispecific antibody, as monotherapy in the neoadjuvant/adjuvant (perioperative) treatment of resectable microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colon cancer.

This marks a significant new indication for cadonilimab beyond gastric, lung, and cervical cancers, and represents the 13th Phase III/registrational study of the therapy conducted globally. Cadonilimab has moved from later-line to first-line treatment of advanced disease and is now being evaluated in the perioperative setting, further broadening its clinical footprint in immuno-oncology (IO) 2.0.

Colorectal cancer is among the malignancies with the highest incidence and mortality worldwide, with colon cancer accounting for most cases. Perioperative outcomes are a major determinant of long-term prognosis. Patients with MSI-H/dMMR colon cancer derive limited benefit from conventional perioperative chemotherapy, with pathological response rates of only approximately 7%—a persistent and significant unmet medical need.

In metastatic MSI-H/dMMR colorectal cancer, immune checkpoint inhibitors are already established as the standard of care. In localized disease, perioperative treatment holds the potential for curative intent and the prospect of durable clinical cure—an area of substantial clinical importance and patient value. While multiple exploratory studies of PD-(L)1 monoclonal antibodies in this setting have shown encouraging efficacy signals, no immunotherapy has yet been approved anywhere for the perioperative treatment of localized MSI-H/dMMR colon cancer.

MSI-H/dMMR colon cancer is highly responsive to immunotherapy due to its high tumor mutational burden and inflamed immune microenvironment. However, single-target immune checkpoint inhibitors still leave room for improved outcomes. By dual blockade of the PD-1 and CTLA-4 pathways, cadonilimab is designed to more effectively activate and sustain antitumor immune responses in the perioperative setting. This approach has the potential to increase rates of major pathological response (MPR) and pathological complete response (pCR), thereby lowering the risk of postoperative recurrence and improving long-term survival.

Supporting evidence comes from a prior Phase II study of cadonilimab monotherapy as neoadjuvant treatment in patients with MSI-H/dMMR colorectal cancer. Data presented at the 2024 ESMO Immuno-Oncology Congress showed a pathological complete response (pCR) rate of 84.6% and a major pathological response (MPR) rate of 100% among patients who proceeded to surgery, with a manageable safety profile.

As the first approved checkpoint bispecific antibody for cancer, cadonilimab has shown consistent clinical benefit across a broad range of patients, including both PD-L1-positive and PD-L1-negative individuals, in extensive real-world use and multiple Phase III trials. It is increasingly recognized as a foundational therapy in the immuno-oncology (IO) 2.0 era. Cadonilimab is currently being evaluated in 13 Phase III/registrational studies worldwide across major indications such as lung, gastric, cervical, liver and colon cancers, spanning first-line, second-line, perioperative, adjuvant and consolidation settings.