Givastomig with nivolumab and chemotherapy for CLDN18.2-positive metastatic stomach or gastroesophageal junction cancer

A Randomized, Multicenter, Open-Label, Phase 2 Study of Givastomig (TJ033721) in Combination With Nivolumab and Chemotherapy Versus Nivolumab and Chemotherapy in Participants With Previously Untreated CLDN18.2 Positive and PD-1L Positive Locally Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Adenocarcinoma

This study will see if adding givastomig to nivolumab plus standard chemotherapy helps adults with CLDN18.2- and PD-L1-positive metastatic stomach or gastroesophageal junction cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: I-Mab Biopharma US Limited (Industry-sponsored)
• Drugs / interventions: nivolumab, chemotherapy, immunotherapy
• Locations: 3 sites (Goodyear, Arizona and 2 other locations)
• Trial ID: NCT07432295 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase 2 trial comparing two dosing schedules of givastomig combined with nivolumab and chemotherapy versus nivolumab and chemotherapy alone in previously untreated, HER2-negative, CLDN18.2-positive, PD-L1-positive locally advanced or metastatic gastroesophageal adenocarcinoma. About 180 participants will be randomized 1:1:1 to two investigational arms (givastomig + nivolumab + mFOLFOX or CAPOX) or a control arm (nivolumab + chemotherapy), with chemotherapy chosen per local standard (mFOLFOX only in the US, Japan, and South Korea). Randomization is stratified by chemotherapy regimen and CLDN18.2 expression level, and tumor response will be measured by RECIST v1.1 at scheduled intervals. Safety and progression-free survival are primary focuses, with safety monitoring for tivastomig-related toxicities alongside standard adverse event reporting.

Who should consider this trial

Good fit: Adults with previously untreated, unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma that is HER2-negative, CLDN18.2-positive and PD-L1-positive, with ECOG 0–1 and adequate organ function are the intended participants.

Not a fit: Patients with HER2-positive tumors, prior systemic therapy for metastatic disease, poor performance status, or insufficient CLDN18.2/PD-L1 expression are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could extend progression-free survival for patients with CLDN18.2-positive, PD-L1-positive metastatic gastroesophageal adenocarcinoma compared with nivolumab and chemotherapy alone.

How similar studies have performed: Other agents targeting CLDN18.2 combined with chemotherapy (for example, zolbetuximab) have shown positive results, but combining givastomig with nivolumab is a newer approach under study.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed unresectable, locally advanced, or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma (EAC).
* Treatment-naïve for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy allowed if ≥6 months since last dose).
* CLDN18.2 positive (membrane intensity score ≥1+ on ≥1% of tumor cells).
* PD-L1 positive (CPS ≥1).
* At least 1 measurable lesion per RECIST v1.1.
* ECOG performance status 0 or 1.
* Adequate organ function, including:

  * Hematologic: WBC ≥2,000/μL; ANC ≥1,500/μL; platelets ≥100,000/μL; hemoglobin ≥9 g/dL
  * Hepatic: AST/ALT ≤3×ULN (≤5×ULN if liver metastases); bilirubin ≤1.5×ULN (≤3×ULN if Gilbert's)
  * Renal: Creatinine ≤1.5×ULN or eGFR ≥50 mL/min/1.73 m²
* Life expectancy ≥90 days.
* Women of childbearing potential (WOCBP) and men must use effective contraception during the study and for a defined period after treatment.
* Willing and able to provide informed consent and comply with study procedures

Exclusion Criteria:

* HER2-positive tumors.
* Second malignancy within 3 years, except certain skin or cervical cancers.
* Active or unstable gastrointestinal ulcer or bleeding within 6 weeks.
* Active autoimmune disease requiring systemic therapy within past 2 years or ongoing immunosuppressive therapy.
* Active pneumonitis or history requiring steroids/immunosuppressive therapy within 3 years.
* Participation in another therapeutic clinical trial.
* Major surgery or significant injury within 4 weeks prior to first dose, or planned major surgery within 6 months.
* Radiotherapy within protocol-specified timeframes without adequate recovery.
* Active CNS metastases or carcinomatous meningitis (previously treated brain metastases allowed if stable).
* Significant cardiovascular disease (NYHA Class 3-4 CHF, recent MI, unstable angina, TIA/stroke, or major cardiac procedures within 6 months).
* Active or uncontrolled HIV, hepatitis B, or hepatitis C infection, or immunodeficiency (controlled infection allowed).
* Receipt of live vaccine within 30 days or other vaccines within 7 days of first dose.
* Active infection requiring parenteral therapy.
* Known hypersensitivity to study drug components (e.g., DPD deficiency).
* Any other condition or laboratory abnormality that, in the investigator's judgment, increases risk or interferes with study participation.

Where this trial is running

Goodyear, Arizona and 2 other locations

• I-Mab Site 1016 — Goodyear, Arizona, United States (Recruiting)
• I-MAB Site 1005 — Duarte, California, United States (Recruiting)
• I-Mab Site 1013 — Sugarland, Texas, United States (Recruiting)

Study contacts

• Study coordinator: I-MAB US Clinical Trials

Conditions Solid Tumor; Advanced Cancer; Metastatic Cancer; Gastric Cancer; Gastroesophageal Junction Carcinoma; Esophageal Adenocarcinoma