A phase II, multicenter, open-label study (COMPASSION-26) of cadonilimab, a PD-1/CTLA-4 bispecific antibody,combined with chemotherapy (chemo) as first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC)

Background: PDAC is a highly lethal malignancy, with approximately 80% of patients presenting with unresectable locally advanced or metastatic disease at diagnosis. Prognosis for advanced PDAC remains poor, with limited treatment options. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, has shown convincing efficacy with favorable safety profile in Phase 3 trials in gastric cancer and cervical cancer. Herein, we report preliminary efficacy and safety results of cadonilimab plus AG (gemcitabine combined with nab-paclitaxel) as the first-line treatment in patients (pts) with advanced PDAC in a phase 2 study (NCT05859750). Methods: Pts with unresectable advanced or metastatic PDAC and no prior systemic therapy were enrolled. Eligible pts received cadonilimab (6 mg/kg or 10 mg/kg, Q2W) + chemo (AG, Q4W). The primary endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Results: As of 20 Oct 2025, 59 pts were enrolled (median age 63.1 years, 61.0% male, 74.6% ECOG PS 1, 59.3% with distant metastasis). The median follow-up time was 24.7 months (range: 3.0+, 27.4). 56 patients (95%) had at least one post-baseline tumor evaluation. The ORR and disease control rate (DCR) were 33.9% (19/56) and 96.4% (54/56), respectively, with no significant difference between locally advanced or metastatic pts. Longer DoR and survival was observed in the pts with locally advanced diseases. The median DoR was 7.46 months (95%CI: 4.07, NE) vs 4.80 months (95%CI: 1.87, 11.01). The median PFS was 11.1 months (95%CI: 8.7, 15.9) vs 7.2 months (95%CI: 5.5, 7.7). The median OS was 23.4 months (95%CI: 14.9, NE) vs 10.5 months (95%CI: 8.5, 12.8). Treatment-related adverse events (TRAEs) occurred in 100.0% of pts, and the most frequent were neutrophil count decreased (96.6%), anemia (89.8%), white blood cell count decreased (84.7%), platelet count decreased (76.3%), rash (52.5%), alanine aminotransferase increased (49.2%), aspartate aminotransferase increased (47.5%), alopecia (45.8%), lymphocyte count decreased (35.6%), pyrexia (35.6%), asthenia (32.2%), and pruritus (32.2%). No new safety signals were identified. Conclusions: AK104 in combination with AG showed encouraging efficacy and manageable safety in previously untreated pts with advanced PDAC. Table 1. OS and PFS based on RECIST 1.1 by disease status Locally advanced (N = 24 ) Metastatic (N = 35 ) Total (N= 59 ) Median PFS (months) , ( 95% CI ) 11.1 (8.7, 15.9) 7.2 (5.5, 7.7) 8.5 (7.2, 10.4) 6- month PFS Rate (%) , ( 95% CI ) 89.9 (65.3, 97.4) 54.2 (34.2, 70.5) 69.2 (54.0, 80.2) Median OS (months) , ( 95% CI ) 23.4 (14.9, NE) 10.5 (8.5, 12.8) 13.8 (11.5, 17.7) 12- month OS Rate (%) , ( 95% CI ) 91.7 (70.6, 97.8) 40.0 (24.0, 55.5) 61.0 (47.4, 72.1) 24 - month OS Rate (%) , ( 95% CI ) 44.1 (23.5, 62.8) 14.3 (5.2, 27.7) 26.2 (15.6, 38.1)