Neoadjuvant Cadonilimab Combined With Perioperative Oxaliplatin Plus S1 for Diffuse or Mixed Type of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

NCT06949033 | Recruiting Phase 3 DMC

• 1 other identifier: LanzhouU2H-2025A-017
• Study Type: interventional
• Target: 668
• Locations: 1 country
• Sites: 4

Brief Summary

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. 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. 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.
3. 3.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).
4. 4.Control group: Participants will receive a placebo in combination with the SOX regimen.

Conditions

Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Neoadjuvant Therapy; Adjuvant Chemotherapy; pCR Rate; MPR; ORR,OS,PFS

Keywords

gastric cancer; Diffuse or Mixed type; Cadonilimab; Oxaliplatin; S1

Outcome Measures

Primary Outcomes (2)

• 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.

  From enrollment to surgical treatment, it is expected to require 4 months.

• 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.

  3 years

Secondary Outcomes (10)

• Major pathological response (MPR) rate

  From enrollment to surgical treatment, it is expected to require 4 months.

• Objective response rate (ORR)

  From enrollment to preoperative imaging evaluation, it is expected to require 3-4 months.

• Treatment emergent adverse event

  From enrollment to the completion or discontinuation of treatment, an estimated duration of eight months is expected.

• Disease control rate (DCR)

  From enrollment to preoperative imaging evaluation, it is expected to require 3-4 months.

• 3-year BICR-assessed disease-free survival (DFS) rate

  3 years

Study Arms (2)

Neoadjuvant cadonilimab combined with perioperative SOX group

EXPERIMENTAL

Participants will receive intravenous cadonilimab (10 mg/kg) in combination with the SOX regimen (oxaliplatin 130 mg/m² and S-1 at a dose of 40-60 mg/m²) for a total of three or four cycles. Subsequently, patients will undergo radical surgery with D2 or D2+ lymphadenectomy. Adjuvant chemotherapy will commence on the 21st or 42st day after surgery, consisting of four cycles of SOX chemotherapy in both groups, administered once every three weeks.

Drug: Neoadjuvant cadonilimab combined with perioperative SOX

Neoadjuvant placebo plus perioperative SOX

PLACEBO COMPARATOR

Participants will receive intravenous placebo in combination with the SOX regimen (oxaliplatin 130 mg/m² and S-1 at a dose of 40-60 mg/m²) for a total of three or four cycles. Subsequently, patients will undergo radical surgery with D2 or D2+ lymphadenectomy. Adjuvant chemotherapy will commence on the 21st or 42st day after surgery, consisting of four cycles of SOX chemotherapy in both groups, administered once every three weeks.

Drug: Neoadjuvant placebo plus perioperative SOX

Interventions

Neoadjuvant cadonilimab combined with perioperative SOX DRUG

Cadonilimab: 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 cadonilimab combined with perioperative SOX group

Neoadjuvant placebo plus perioperative SOX DRUG

Placebo: 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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Demographics
• Male or female subjects must be between the ages of ≥ 18 and ≤ 75 years at the time of signing the informed consent.
• Expected Survival: The expected survival time must be ≥ 12 weeks.
• Performance Status: Subjects must have an ECOG performance status of 0 or 1 (refer to Appendix 1).
• Male Contraception: Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use an effective method of contraception from Day 1 through 120 days after receipt of the final dose of the investigational product. It is strongly recommended for the female partner of a male subject to also use an effective method of contraception throughout this period.
• Female subjects of childbearing potential must be willing to use adequate contraception methods throughout the study and for 120 days after the last dose of the study drug. The decision to discontinue contraception after this time point should be discussed with the attending physician. Periodic abstinence, contraceptive rhythm methods, and withdrawal are not acceptable forms of contraception.
• Females of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
• Highly effective contraception methods, resulting in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, are required. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plus spermicide) to prevent pregnancy.
• Barrier methods include male condom plus spermicide, copper T intrauterine device, and levonorgestrel-releasing intrauterine system.
• Hormonal methods include implants, hormone injection, combined pill, minipill, and patch.
• If a female subject becomes pregnant or suspects pregnancy during her participation in the study or her partner's participation, she must promptly inform her treating physician.

You may not qualify if:

• 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.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. (NOTE: Subjects with vitiligo, alopecia, Grave's disease, Type I diabetes mellitus, hypothyroidism (e.g., following Hashimoto's syndrome) only requiring hormone replacement on a stable dose (without adjustment in the first 4 weeks of study treatment), psoriasis or eczema not requiring systemic treatment (within the past 2 years), or conditions not expected to recur in the absence of an external trigger are not excluded.)
• Has any complications requiring systemic treatment with corticosteroids such as prednisone (\> 10mg/day) or other immunosuppressive medications within 14 days prior to the first administration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
• History of primary immunodeficiency.
• Has received a live vaccine or other immune-activating anti-tumor drugs (such as interferon, interleukin, thymosin, or immunotherapy) within 30 days prior to the first dose of study treatment.
• Has a known history of active tuberculosis.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Has a known severe allergy or hypersensitivity to cadonilimab or sintilimab or any of the study chemotherapy agents and/or to any of their excipients.
• Presence of any of the following cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors:
• Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥ 480 ms), grade III or IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) \< 50.0% as determined by color Doppler echocardiography.
• Cerebrovascular accident, transient ischemic attack, or other arteriovenous thrombotic, embolic, or ischemic events.
• Prior/Concomitant Therapy

Sponsors & Collaborators

• Zuoyi Jiao: lead

Study Sites (4)

Gansu Provincial Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

Lanzhou University Second Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

RECRUITING

The Gastrointestinal Surgery Department, Sun Yat-sen University Cancer Center Gansu Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Bo Long

CONTACT

+86 130 0878 1208; longbo_107@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Professor

Study Record Dates

• First Submitted: March 30, 2025
• First Posted: April 29, 2025
• Study Start: May 15, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)