1455P - Chemotherapy combined with cadonilimab (AK104) as neoadjuvant treatment for locally advanced gastric/gastroesophageal junction cancer: A prospective, single-arm, phase II clinical trial

Background

Neoadjuvant chemotherapy combined with PD-1 or PD-L1 antibodies is being extensively studied in locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the effect of PD-1/CTLA-4 bispecific antibody combined chemotherapy has not been reported. The study evaluated the efficacy and safety of chemotherapy combined with cadonilimab, a PD-1/CTLA-4 bispecific antibody, in neoadjuvant therapy for locally advanced G/GEJ cancer.

Methods

In this ongoing, single-arm, phase 2 study, 37 patients with locally advanced G/GEJ cancer (cT3-4a N+ M0, CY0, P0) will be enrolled and treated with 3 cycles of SOX (oxaliplatin plus S-1) combined with cadonilimab, followed by radical D2 gastrectomy. The primary endpoint was pathological complete response (pCR) rate and the secondary endpoints were R0 resection rate, major pathological response (MPR), 2-year disease-free survival (DFS), 2-year overall survival (OS) and safety.

Results

From September 2023 to April 2024, a total of 24 patients were enrolled, with median age 58.5 years (range 27-72). 19 (79.2%) patients were with primary tumor location in the stomach, and 5 (20.8%) patients were with primary tumor location in the GEJ. 7 (29.2%) patients were cT3 and 17 (70.8%) were cT4. 14 patients have undergone preoperative evaluation. One patient refused surgery. 13 patients experienced D2 gastrectomy and all achieved R0 resection. 4 patients (30.8%) achieved pCR (TRG 0). Common treatment-related adverse events (TRAEs) were nausea (66.7%), fatigue (62.5%), vomiting (62.5%), neutropenia (50.0%), AST increase (41.7%), anemia (37.5%), ALT increase (37.5%), thrombocytopenia (37.5%), leukopenia (29.2%) and diarrhea (12.5%). The potential immune-related adverse events (irAEs) were dermatitis (29.2%) and hypothyroidism (8.3%). Grade3 TRAEs and irAEs included thrombocytopenia (16.7%), hyperglycemia (4.2%) and ALT increase (4.2%).

Conclusions

SOX plus cadonilimab showed encouraging pCR rate and manageable safety, which provided a new neoadjuvant option for locally advanced gastric cancer. The study is still enrolling, and the survival effects are under follow up.

Clinical trial identification

NCT05948449.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Akeso, Inc.

Disclosure

All authors have declared no conflicts of interest.