Neoadjuvant cadonilimab plus CapeOX in patients with clinical stage III gastric or esophagogastric junction adenocarcinoma (GC/EGJC): A prospective, single-arm phase II study.

Abstract

4089 Background: Perioperative PD-L1 inhibitor plus chemotherapy has shown survival benefit in PD-L1-positive patients with locally advanced GC/EGJC. However, evidence for neoadjuvant PD-1/CTLA-4 bispecific blockade remains limited. This study evaluates neoadjuvant cadonilimab plus CapeOX in patients with clinical stage III GC/EGJC. Methods: This prospective, single-arm phase II study (NCT06310473) enrolled patients (pts) with cT3-4aN1-3M0 disease (AJCC 8th), staged by contrast-enhanced CT and staging laparoscopy with peritoneal cytology to exclude peritoneal metastasis and positive peritoneal cytology (CY1). Pts received cadonilimab (10 mg/kg) plus standard-dose CapeOX every 3 weeks for 3 cycles. Pts without progressive disease on repeat CT and laparoscopy underwent curative-intent surgery, followed by 3-5 cycles of adjuvant CapeOX. The primary endpoint was the pathologic complete response rate (pCR, defined as no residual tumor in stomach and lymph node). The data cutoff was January 15, 2026. Results: From May 2024 to August 2025, 30 pts with GC/EGJC were enrolled (GC, n = 21; EGJC, n = 9); 83.3% (25/30) were cT4a and 73.3% (22/30) were cN2-3. PD-L1 CPS < 1 was observed in 14.8% (4/27) of evaluable pts. All pts completed 3 neoadjuvant cycles. Three pts did not undergo surgery: one refused resection and subsequent antitumor therapy after achieving a cCR to neoadjuvant therapy; one had a PR and continued systemic therapy; and one had PD with liver invasion on repeat laparoscopy and initiated second-line therapy. The other 27 pts underwent resection; one had CY1 on postoperative assessment and was considered PD, with an R0 resection rate of 96.3% (26/27). The pCR and major pathologic response (MPR) rates were 22.2% (6/27) and 37.0% (10/27), respectively. The tumor downstaging rate was 74.1% (20/27), including a ypN0 rate of 55.6% (15/27). Adjuvant therapy was administered in 23/27 (85.2%), with four pts still on therapy. Treatment-related adverse events occurred in 100% (30/30), including grade≥3 events in 20.0% (6/30). Notable events included one perioperative cardiovascular death (G5); one pulmonary embolism (G3) diagnosed 5 weeks postoperatively that resolved with anticoagulation; one patient with concomitant anastomotic leakage (G4), intra-abdominal infection (G4), and immune-related adrenal insufficiency (G2) who recovered after endoscopic covered-stent placement and conservative management; additional G3 events included ascites, neutropenia, and peripheral neuropathy (n = 1 each). No postoperative recurrence was observed among resected pts at data cutoff. Conclusions: Neoadjuvant cadonilimab plus CapeOX appears safe and effective in patients with clinical stage III GC/EGJC, achieving a moderate pCR rate and warranting further exploration of neoadjuvant immunochemotherapy combination strategies. Clinical trial information: NCT06310473 .