Akeso, A first patient has been dosed in a phase 3 clinical study evaluating cadonilimab by Akeso Inc, 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 3/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 localised 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 localised 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.
