Clinical Study of Adebrelimab Therapy in the Perioperative Treatment of Gastric Cancer or Gastroesophageal Junction Cancer

Official title

A Randomized, Double-blind, Multicenter Phase III Trial of Adebrelimab (SHR-1316) Plus S-1 and Oxaliplatin (SOX) Versus Placebo Plus S-1 and Oxaliplatin in the Perioperative Treatment of Resectable Gastric or Gastroesophageal Junction Cancer

Overview

This study was a randomized, double-blind, multi-center phase III clinical trial to evaluate the event-free survival (EFS) of Adebrelimab with S-1 and oxaliplatin versus placebo combined with S-1 and oxaliplatin, and to evaluate the efficacy, safety and tolerability of the two combination regimens.

Interventions

• Drug Adebrelimab plus S-1 and oxaliplatin
  Adebrelimab plus S-1 and oxaliplatin
• Drug Adebrelimab blank preparation plus S-1 and oxaliplatin.
  Adebrelimab blank preparation plus S-1 and oxaliplatin.

Primary outcome measures

• Investigator-assessed EFS [Time frame: About 8 years]

Secondary outcome measures (10)

• Complete response (pCR) rate as assessed by the Pathology Review Committee (PRC) [Time frame: About 3 years]
• Rate of pathologically significant response (MPR) as assessed by the Pathology Review Committee (PRC) [Time frame: About 3 years]
• EFS as assessed by an independent review committee (IRC) [Time frame: About 8 years]
• DFS, as assessed by investigator /IRC [Time frame: About 8 years]
• pCR rate by central pathological evaluation [Time frame: About 3 years]
• R0 resection rate of neoadjuvant therapy evaluated by investigators in different treatment groups [Time frame: About 8 years]
• D2 radical resection rate of neoadjuvant therapy evaluated by investigators in different treatment groups [Time frame: About 8 years]
• objective response rate (ORR) of neoadjuvant therapy evaluated by investigators in different treatment groups [Time frame: About 8 years]
• The incidence of adverse events (AE) were evaluated according to NCI-CTCAE 6.0 [Time frame: About 4 years]
• The severity of serious adverse events (SAE) were evaluated according to NCI-CTCAE 6.0 [Time frame: About 4 years]

Eligibility criteria

Inclusion criteria

• Patients with pathologically confirmed gastric cancer or gastroesophageal junction cancer.
• Age: ≥18 years old, <75 years old, both male and female are eligible.
• Before entering the study, the investigator has evaluated and determined that the subject is suitable and plans to undergo neoadjuvant therapy + radical surgery for curative purposes.
• Gastric cancer or gastroesophageal junction cancer applicable to the 8th edition of the AJCC gastric cancer staging criteria.
• Fresh specimens (preferred) or formalin-fixed, paraffin-embedded tumor tissue blocks or unstained tumor specimen sections obtained within 6 months before randomization can be provided.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1.
• Expected survival ≥ 6 months.
• Adequate organ and bone marrow function.
• Female subjects are either infertile or fertile, with a negative serum pregnancy test result within 3 days before the start of study medication and not in the lactation period. Fertile female subjects and male subjects whose partners are fertile must agree to avoid sperm/egg donation from the time of signing the informed consent form until 6 months after the last administration of the investigational drug, and comply with relevant contraceptive requirements.
• Consent has been obtained from the individual and the informed consent form has been signed, willing and able to comply with planned visits, study treatment, laboratory tests, and other trial procedures.

Exclusion criteria

• Gastric cancer known to be squamous cell carcinoma, undifferentiated carcinoma or other histological types, or adenocarcinoma mixed with other histological types.
• Gastric esophageal junction cancer, Siewert type I; or Siewert type II with esophageal invasion length ≥ 4 cm; or other cases not suitable for clinical staging assessment using the 8th edition of the AJCC gastric cancer staging criteria, or not suitable for conventional surgical methods or approaches for gastric cancer.
• The subject's weight has decreased by more than 20% within 2 months before randomization.
• Previous anti-tumor treatment for gastric cancer/gastric esophageal junction cancer (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biological therapy or tumor embolization).
• Known allergy to any component of the investigational drug (including adibelimab/placebo, tegafur, and oxaliplatin), or allergy to humanized monoclonal antibody products.
• Diagnosis of any other malignant tumor within 5 years before entering the study, except for locally treatable and cured skin basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
• History of immunodeficiency (including positive HIV test, other acquired or congenital immunodeficiency diseases) or organ transplantation (including allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, etc.); history of active autoimmune disease, except for immune disorders that do not require systemic treatment (such as vitiligo, psoriasis, etc.) or autoimmune diseases that can be improved through hormone replacement therapy (such as type 1 diabetes or hypothyroidism).
• Severe, unhealed or open wounds, active ulcers, or untreated fractures.
• Active severe digestive system diseases.
• Presence of interstitial pneumonia or interstitial lung disease.
• Severe cardiovascular or metabolic diseases.
• Active HBV or HCV infection (HBsAg positive and viral copy number ≥ 2000 IU/mL, HCV antibody positive and HCV RNA above the upper limit of normal at the research center), or co-infection with hepatitis B and hepatitis C.
• Active tuberculosis infection within 1 year before randomization (including but not limited to pulmonary tuberculosis, intestinal tuberculosis, etc.), or a history of active tuberculosis infection more than 1 year ago but without regular treatment.
• Severe infection within 4 weeks before randomization.
• Known history of abuse of psychotropic drugs or drug addiction.
• Presence of other serious physical or mental diseases or abnormal laboratory tests that may increase the risk of participation in the study, or interfere with the study results, and patients considered unsuitable for participation in the study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT07522151 · SHR-1316-309

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗