This study aims to investigate the efficacy and safety of neoadjuvant cadonilimab in combination with perioperative SOX chemotherapy, compared to perioperative SOX chemotherapy alone, in patients with diffuse or mixed-type locally advanced gastric or gastroesophageal junction adenocarcinoma. The main questions it seeks to answer are:
1. Is neoadjuvant cadonilimab plus SOX chemotherapy superior to neoadjuvant placebo plus SOX chemotherapy in terms of the pathological complete response (pCR) rate at the time of surgery? 2. To evaluate and compare the 3-year OS rate in patients receiving neoadjuvant cadonilimab plus SOX chemotherapy versus patients receiving placebo plus neoadjuvant SOX chemotherapy regimen.
Participants will be divided into two groups:
1. Experimental group: Participants will receive intravenous cadonilimab (10 mg/kg) in combination with the SOX regimen (oxaliplatin 130 mg/m² and S-1, with the initial dose determined based on body surface area). 2. Control group: Participants will receive a placebo in combination with the SOX regimen.
After completing 3-4 cycles of treatment, patients in both the experimental and control groups will undergo radical surgery with D2 or D2+ lymphadenectomy. Following surgery, patients will receive 4 cycles of adjuvant SOX chemotherapy at 70% of the standard dosage, administered every 21 days, starting within 3-6 weeks post-surgery.
Type of Participant and Disease Characteristics
Patients must have a pathologically confirmed diagnosis of HER-2 negative tumor and diffuse or mixed type gastric or gastroesophageal junction adenocarcinoma according to Lauren's histological subtypes.
Patients must have previously untreated locally advanced gastric or gastroesophageal junction adenocarcinoma (stage cT2, cT3, cT4), with lymph nodes ranging from N1 to N3 and no evidence of metastatic disease (M0).
Patients with Siewert type 2 or 3 tumors are eligible. Enrollment of participants with Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection.
Medical Conditions
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years (except for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ that has undergone potentially curative therapy).
Has an active infection requiring systemic therapy.
Parallel
Neoadjuvant cadonilimab combined with perioperative SOX
DrugCadonilimab: 10 mg/kg, iv, day 1 of every 3 weeks Oxaliplatin: 130 mg/m², iv, day 1 of every 3 weeks S1: 40-60 mg/m², po, day 1-14 of every 3 weeks (BSA \< 1.25 m², 40 mg \* 2/day, 1.25 m² ≤ BSA \< 1.5 m², 50 mg \* 2/day, BSA ≥ 1.5 m², 60 mg \* 2/day)
Neoadjuvant placebo plus perioperative SOX
DrugPlacebo: iv, day 1 of every 3 weeks Oxaliplatin: 130 mg/m², iv, day 1 of every 3 weeks S1: 40-60 mg/m², po, day 1-14 of every 3 weeks (BSA \< 1.25 m², 40 mg \* 2/day, 1.25 m² ≤ BSA \< 1.5 m², 50 mg \* 2/day, BSA ≥ 1.5 m², 60 mg \* 2/day)
Pathological complete response (pCR) rate
The pCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes as assessed by BIPR based on Becker regression criteria. pCR rate is defined as the proportion of participants having pCR.
3-year survival rate (3-year OS rate)
3-year OS rate is defined as the proportion of patients alive at 3 years after randomization estimated using the Kaplan-Meier method. Participants without documented death at the time of analysis will be censored at the date of last known alive.
Major pathological response (MPR) rate
MPR rate by BIPR is defined as the proportion of patients with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant therapy as assessed by BIPR.
Objective response rate (ORR)
ORR is defined as the proportion of patients who had complete response (CR) or partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in all randomized patients with measurable disease at baseline.
Treatment emergent adverse event
Incidence and severity of TEAEs, including serious adverse events (SAEs) and immune-mediated adverse events (imAEs), with severity determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
Disease control rate (DCR)
DCR is defined as the proportion of patients who had CR, PR or stable disease (SD) as assessed by BICR per RECIST v1.1 in all randomized patients with measurable disease at baseline.
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Zuoyi Jiao
Lead sponsor
Lanzhou University Second Hospital
Sponsor institution
