Testing Two Immunotherapy Drug Combinations Before Surgery for Stomach Cancer

Trial details

Who runs it

Qun Zhao

Trial code

NCT07924332

Record updated

9 November 2026

Original description

This multicenter, randomized, open-label, exploratory phase II study aims to evaluate the efficacy and safety of perioperative Retlirafusp Alfa plus SOX versus adebrelimab plus SOX in adult patients with previously untreated, HER2-negative, resectable locally advanced gastric or gastroesophageal junction adenocarcinoma (clinical stage II-III, AJCC 8th edition).Read full original descriptionShow less

A Randomized, Exploratory Phase II Study of Retlirafusp Alfa or Adebrelimab Combined With SOX as Neoadjuvant Therapy for HER2-Negative Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

This multicenter, randomized, open-label, exploratory phase II study aims to evaluate the efficacy and safety of perioperative Retlirafusp Alfa plus SOX versus adebrelimab plus SOX in adult patients with previously untreated, HER2-negative, resectable locally advanced gastric or gastroesophageal junction adenocarcinoma (clinical stage II-III, AJCC 8th edition).

Approximately 98 participants will be randomized at a 1:1 ratio via stratified block randomization. Stratification factors include tumor location (gastric versus gastroesophageal junction) and PD-L1 combined positive score (CPS <1 versus CPS ≥1).

Participants will receive 3 preoperative cycles of assigned immunotherapy combined with SOX, followed by D2 radical gastrectomy performed 4-8 weeks after the last neoadjuvant cycle. Postoperatively, participants will receive 5 cycles of the same immunotherapy plus SOX, then up to 9 cycles of immunotherapy monotherapy, with a maximum of 17 total immunotherapy cycles.

The primary outcome measure is pathologic complete response (pCR) rate. Secondary outcome measures include R0 resection rate, event-free survival, disease-free survival, overall survival, surgical safety, adverse events, laboratory abnormalities, and treatment tolerability.

Inclusion: Voluntary signed written informed consent; Age ≥ 18 years; Histologically-confirmed gastric / gastroesophageal junction adenocarcinoma; Siewert II / III are eligible; Resectable clinical stage II-III (cT1-2N+M0, cT3-4aNanyM0, AJCC 8th edition) confirmed by CT / MRI; No prior anti-cancer therapy (surgery, radiotherapy, chemotherapy, targeted or immunotherapy); Investigator-assessable for R0 resection; planned curative surgery after neoadjuvant therapy; Able to swallow oral tablets; ECOG-PS 0-1; Available PD-L1 CPS result or 3-5 unstained tumor slides for testing (fresh or pre-randomization FFPE tissue acceptable); Estimated life expectancy ≥ 12 months; Adequate organ function (no transfusion / G-CSF in prior 14 d):; ANC ≥ 1.5 × 10⁹/L; platelets ≥ 80 × 10⁹/L; Hb ≥ 90 g/L; Total bilirubin < 1.5 × ULN; ALT/AST ≤ 2.5 × ULN; Serum Cr ≤ 1.5 × ULN or CrCl > 50 mL/min; Women of child-bearing potential: negative serum pregnancy test ≤ 72 h pre-randomization; effective contraception (longer of 3 months post-last retlirafusp alfa / adebrelimab or 6 months post-chemotherapy). Fertile-partner males: surgical sterility or same contraception window; no sperm donation during study.

Exclusion: Anticipated transthoracic surgical approach; Gastrointestinal obstruction signs/symptoms within prior 6 months (except symptoms resolved by definitive surgery); GI perforation or fistula within prior 6 months; Arterial / venous thromboembolic event within prior 6 months (superficial phlebothrombosis excluded); Major vascular disease within prior 6 months; Prior or planned organ / allogeneic bone-marrow transplantation; Systemic immunosuppressive corticosteroids (>10 mg prednisone-equivalent daily) within 7 days pre-randomization; Live-attenuated vaccine within 28 days pre-randomization or planned during-/within 60 days post-study-treatment; Investigational-drug clinical trial participation within prior 4 weeks; Unresectable disease, surgical contraindication or refusal of surgery; Other malignancy within 5 years (exception: cured basal-cell skin, cervical / breast carcinoma-in-situ); Laparoscopy shows peritoneal metastasis, positive peritoneal cytology (CY1P0) or AJCC 8th T4b disease; Clinically-significant bleeding tendency within 3 months pre-randomization. Persistently positive fecal occult blood requires gastroscopy; Hereditary / acquired bleeding or thrombotic diathesis; Active ulcer, unhealed wound or fracture; CTCAE>grade 2 severe infection within 4 weeks pre-randomization; active pulmonary inflammation; ongoing need for systemic antibiotics (≤48 h prophylactic IV antibiotics permitted); Active hepatitis B (HBsAg+ plus HBV-DNA ≥ 2000 IU/mL) or active hepatitis C; Congenital / acquired immunodeficiency including HIV infection; Interstitial lung disease / pneumonitis (current or steroid-treated history); pulmonary fibrosis, pneumoconiosis, active tuberculosis or severe pulmonary impairment on screening CT; Active autoimmune disease or high-risk relapse history (exceptions: hormone-replaced hypothyroidism; controlled type 1 diabetes; stable vitiligo, psoriasis, resolved childhood asthma; asthma requiring bronchodilators is excluded); Hypersensitivity to any study drug or excipients; Investigator-judged other conditions interfering with study conduct or participant safety (substance abuse, severe psychiatric illness etc); Cardiac abnormalities: NYHA ≥ II heart failure or LVEF < 50 %; unstable angina; MI within 1 year; QTc prolongation (male>450 ms, female>470 ms); significant ECG abnormality / high-grade AV-block / PR>250 ms; risk factors for QTc prolongation; Coagulopathy (INR>2.0, PT>16 s), bleeding diathesis or ongoing thrombolytic / anticoagulant therapy (prophylactic low-dose aspirin / LMWH allowed); Known HER2-positive tumor; Pregnancy, lactation or planned pregnancy during study treatment.

ClinicalTrials.gov NCT07924332