IBI343 plus sintilimab and chemotherapy for CLDN18.2-positive gastric or gastroesophageal junction cancer

IBI343 Combined With Sintilimab Plus Chemotherapy in Previously Untreated, Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Dragon15)

This trial tests IBI343 combined with sintilimab and standard chemotherapy as a first-line treatment for adults with CLDN18.2-positive, HER2-negative advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (other)
• Drugs / interventions: Sintilimab, Chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07025889 on ClinicalTrials.gov

What this trial studies

This open-label phase 1b/2 trial combines IBI343 with the PD‑1 inhibitor sintilimab and chemotherapy (oxaliplatin plus S‑1) in previously untreated, CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma. A 3+3 dose-escalation stage identifies the recommended phase II dose, followed by dose-expansion cohorts including 25 patients in a general CLDN18.2-positive cohort and 15 patients with signet-ring cell histology. The study’s primary aims are to characterize safety and tolerability and to generate preliminary efficacy data including response rates and progression-free survival. Key eligibility includes age 18–75, ECOG 0–1, no prior systemic therapy, and confirmed CLDN18.2-positive, HER2-negative disease.

Who should consider this trial

Good fit: Adults aged 18–75 with untreated, unresectable locally advanced or metastatic CLDN18.2-positive, HER2-negative gastric or GEJ adenocarcinoma and ECOG performance status 0–1.

Not a fit: Patients with HER2-positive tumors, prior systemic therapy for advanced disease, prior topoisomerase inhibitor–based ADCs, or poor performance status (ECOG >1) are unlikely to be eligible or benefit.

Why it matters

Potential benefit: If effective, this combination could improve response rates and lengthen disease control for patients with CLDN18.2-positive, HER2-negative advanced gastric or GEJ cancer.

How similar studies have performed: Other CLDN18.2-directed therapies (for example zolbetuximab) and PD‑1 inhibitor plus chemotherapy combinations have shown promising activity in gastric cancer, but the specific IBI343 plus sintilimab combination is relatively novel.

Eligibility criteria

Inclusion Criteria:

* 1\. Able and willing to sign a written Informed Consent Form (ICF) and to comply with protocol-specified visits and related procedures.

  2\. Age was 18-75 years at the time of signing the ICF, and gender was unlimited.

  3\. Has histopathologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the gastric/gastroesophageal junction (G/GEJ AC).

  4\. No received systemic therapy. 5. Has histopathologically confirmed CLDN18.2-positive disease. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Exclusion Criteria:

* 1\. Has HER2-positive (defined as immunohistochemistry \[IHC\] 3+, or IHC 2+ and positive by in situ hybridization) disease.

  2\. Is currently participating in another interventional clinical study, except when the subject is during survival follow-up of an interventional clinical study.

  3\. Has a history of treatment with topoisomerase inhibitor-based antibody-drug conjugate(s).

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Min Shi, MD — Ruijin Hospital
• Study coordinator: Ruijin Hospital, Shanghai Jiao Tong University School of Medic

Conditions: Gastric Cancer, IBI 343, Sintilimab