Case Report: Converting an immunologically "cold" tumor: exceptional response to cadonilimab plus chemotherapy in...

Pancreatic cancer (PC) remains largely refractory to immune checkpoint inhibitors (ICIs), especially in the prevalent microsatellite-stable (MSS) subtype. However, combination strategies of ICIs with chemotherapy have largely failed in MSS PC, highlighting an urgent need for novel immunotherapeutic approaches. Cadonilimab is a novel programmed death protein 1(PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) bispecific antibody designed to remodel the immunosuppressive tumor microenvironment.

We report an exceptional and durable response to cadonilimab plus chemotherapy in a patient with metastatic MSS pancreatic cystadenocarcinoma (PCAC). Microsatellite stability was shown by immunohistochemistry with intact expression of all four mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) and confirmed by next-generation sequencing (NGS). Following disease progression on first-line gemcitabine/nab-paclitaxel and transarterial chemoembolization (TACE), the patient subsequently received second-line therapy with cadonilimab combined with nab-paclitaxel and oxaliplatin. Notably, within two months of treatment initiation, the patient achieved near-complete remission (near-CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, with an 89.9% reduction in the sum of target lesion diameters. Despite discontinuing anticancer therapy after 4 cycles due to grade 3 bone marrow suppression, which subsequently evolved into and has been maintained as a complete response (CR) for over 30 months, with the primary endpoint of progression-free survival (PFS) not yet reached.

This case provides pioneering clinical evidence that cadonilimab, in combination with chemotherapy, can induce profound and durable remission in MSS PCAC, challenging current paradigms of ICI resistance and supporting the further development of bispecific antibody strategies.