Conventional perioperative chemotherapy produces a pathological complete response in roughly 7% of patients with MSI-H or mismatch repair-deficient colon cancer. Akeso’s Phase III study COMPASSION-40 is built on the premise that dual PD-1/CTLA-4 blockade can do far better, and a Phase II dataset suggests it might: among patients with MSI-H/dMMR colorectal cancer who received cadonilimab as neoadjuvant monotherapy and proceeded to surgery, 84.6% achieved a pathological complete response and 100% achieved a major pathological response, results presented at the 2024 ESMO Immuno-Oncology Congress. That gap between 7% and 84.6% is what Akeso is now stress-testing in a registrational setting.
The trial enrolled its first patient on October 10, evaluating cadonilimab as monotherapy in the neoadjuvant and adjuvant treatment of resectable MSI-H/dMMR colon cancer. The design targets the perioperative window deliberately: in localized disease, achieving deep pathological responses before and after surgery carries the possibility of durable cure rather than simply slowing progression. MSI-H/dMMR tumors are particularly immunogenic, driven by high tumor mutational burden and an inflamed microenvironment, which is why checkpoint inhibitors are already standard in the metastatic setting. The open question is whether dual-pathway blockade adds meaningfully over PD-(L)1 monotherapy in the localized, perioperative context, where no immunotherapy has yet cleared a regulatory bar anywhere in the world.
COMPASSION-40 is the 13th Phase III or registrational study of cadonilimab running globally, and the first to test the agent in a perioperative colon cancer setting. Cadonilimab holds approvals in China for relapsed or metastatic cervical cancer and for first-line gastric or gastroesophageal junction adenocarcinoma in combination with chemotherapy, and a 2025 approval for persistent, recurrent, or metastatic cervical cancer. The colon cancer program is a structural step toward earlier treatment lines and, for some patients, a shot at resection with curative intent rather than lifelong systemic therapy.
The number to watch as this trial matures is pCR rate at surgery. If COMPASSION-40 replicates something close to the Phase II signal in a randomized, registrational design, it would give the first Phase III-level evidence for an immunotherapy in perioperative MSI-H/dMMR colon cancer, a population that has derived almost no benefit from the chemotherapy regimens still in routine use today.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
