Perioperative cadonilimab (AK104) in locally advanced MSI-H/dMMR gastric or gastroesophageal junction adenocarcinoma and colorectal adenocarcinoma: A basket study.

Abstract

4102 Background: Microsatellite instability-high (MSI-H) / deficient mismatch repair (dMMR) tumors generate abundant neoantigens and are sensitive to PD-1 blockade. However, evidence supporting the use of PD-1/CTLA-4 blockade in the neoadjuvant setting for MSI-H/dMMR gastric and colorectal cancers remains scarce. Methods: In this multicenter, single-arm, dual-cohort basket study (NCT04556253), we used a Simon’s two-stage design to evaluate perioperative cadonilimab in patients with locally advanced MSI-H/dMMR gastric/gastroesophageal junction (GEJ) or colorectal adenocarcinoma. 29 patients were enrolled in cohort 1 (gastric/GEJ adenocarcinoma) and 18 patients were enrolled in cohort 2 (colorectal adenocarcinoma). The main inclusion criteria include newly diagnosed, histologically confirmed cT3–T4aNxM0 MSI-H/dMMR gastric/GEJ adenocarcinoma or colorectal adenocarcinoma, with an ECOG score of 0-1. Both cohorts received 3 cycles of neoadjuvant cadonilimab (10 mg/kg q3w) followed by radical resection, then 6 cycles of adjuvant cadonilimab (6 mg/kg q3w). The primary endpoint was pathologic complete response (pCR). Secondary endpoints included overall survival (OS), event-free survival (EFS), disease-free survival (DFS), major pathologic response (MPR) rate and incidence of adverse events (AEs). Results: As of the data cutoff date of January 24, 2026, the median follow-up was 14.6 months for cohort 1 and 12.6 months for cohort 2. In cohort 1, 2 patients were pathologically confirmed as pMMR prior to treatment. Among the 26 patients (mITT population), pCR rate was 69.2% (95% CI: 48.2%-85.7%), and MPR rate was 80.8% (95% CI: 60.6%-93.4%). The 12-month OS, EFS, and DFS rates were each 100% in mITT population. All 29 patients (ITT population) received neoadjuvant therapy. AEs during neoadjuvant treatment occurred in 24 patients (82.8%), with 3 patients (10.3%) experiencing grade 3-4 AEs. Common AEs (incidence ≥10%) included rash, anemia, constipation, and insomnia, which were primarily grade 1-2. Among the 18 patients (mITT population) in cohort 2, the postoperative pCR rate was 66.7% (95% CI: 41.0%-86.7%), and the MPR rate was 72.2% (95% CI: 46.5%-90.3%). The 12-month OS, EFS, and DFS rates were each 100% in mITT population. All 18 patients (ITT population) received neoadjuvant therapy. AEs during neoadjuvant treatment occurred in 17 patients (94.4%), with 2 patients (11.1%) experiencing grade 3-4 AEs. Common AEs (incidence ≥10%) included rash, infusion-related reaction, anemia, and cough, which were primarily grade 1. No grade 5 AEs were reported in this study. Conclusions: Perioperative cadonilimab demonstrates excellent antitumor activity and a manageable safety profile in patients with locally advanced MSI-H/dMMR gastric/GEJ adenocarcinoma and colorectal adenocarcinoma. Clinical trial information: NCT04556253 .