Givastomig Combined With Nivolumab and Chemotherapy in Adults With CLDN18.2 Positive Metastatic Gastric Cancer (GIVA-2)

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

The goal of this clinical trial is to learn if givastomig in combination with standard therapy works to treat adults with cancer in the stomach and/or esophagus (GEA adenocarcinoma). It will also help the researchers to learn more about the safety of givastomig. The main questions it aims to answer are:

• Does the addition of givastomig to standard therapy increase the amount of time that participants survive without progression of their cancer?
• What toxicities do participants experience when taking givastomig?

Participants may be able to take part in the study if they have unresectable or metastatic GEA and if their cancer cells express certain proteins called Claudin 18.2 (CLDN18.2) and PD-L1. Participants whose cancer cells express a protein called HER2 cannot take part.

Up to 180 participants will be randomly assigned to received givastomig at one of two doses in combination with an immunotherapy medicine called nivolumab and chemotherapy OR to receive nivolumab and chemotherapy alone. These therapies will be given primarily via intravenous (into a vein) infusion every 2 or 3 weeks.

Participants will:

• Visit the study treatment center for infusions and/or check-ups and tests every 1-3 weeks
• Report any changes in their symptoms to their study doctors
• Have scans to check for any changes in their cancer every 8-12 weeks

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Solid Tumor; Metastatic Cancer; Advanced Cancer; Esophageal Adenocarcinoma; Gastroesophageal Junction Carcinoma
• Intervention / Treatment: Drug: Givastomig; Drug: Nivolumab; Drug: 5Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Detailed Description

This is a randomized, global, open-label, multicenter Phase 2 study evaluating the efficacy and safety of givastomig (TJ033721) in combination with nivolumab and chemotherapy compared with nivolumab and chemotherapy alone in participants with previously untreated, HER2-negative, CLDN18.2-positive, and PD-L1-positive locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (GEA).

Approximately 180 participants will be randomized in a 1:1:1 ratio to one of three treatment arms. Two investigational arms will receive givastomig in combination with nivolumab and chemotherapy, and the control arm will receive nivolumab and chemotherapy alone. Chemotherapy will consist of either modified FOLFOX (mFOLFOX) or CAPOX, administered according to local standard of care. Participants enrolled in the United States, Japan, and South Korea will receive mFOLFOX only. Randomization will be stratified by chemotherapy regimen (mFOLFOX vs CAPOX) and by CLDN18.2 expression level (<75% vs ≥75% of tumor cells with membrane intensity score ≥2+).

Participants in the investigational arms will receive givastomig administered every 2 weeks or every 3 weeks, depending on the chemotherapy regimen. Tumor assessments will be performed at protocol-defined intervals and evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Enrollment of participants with high CLDN18.2 expression (defined as membrane intensity score ≥1+ in ≥75% of tumor cells) will be capped at approximately 50% of the total study population. Enrollment of participants receiving CAPOX will be capped at approximately 30% of the total study population.

Study treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, death, or completion of study treatment, whichever occurs first. The duration of chemotherapy treatment will follow the respective product labeling or local standards of care.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: I-MAB US Clinical Trials; Phone Number: 301-294-4408; Email: us.info@imabbio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • I-Mab Site 2001
    • Contact: I-Mab PI - 2001
• Japan
  • Kashiwa, Japan
    • Not yet recruiting
    • I-Mab Site - 4001
    • Contact: I-Mab PI 4001
  • Tokyo, Japan
    • Recruiting
    • I-Mab Site 4005
    • Contact: I-Mab PI - 4005
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Recruiting
      • I-Mab Site 1016
      • Contact: I-Mab PI - 1016
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • I-MAB Site 1005
      • Contact: I-MAB PI - 1005
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • I-Mab Site 1002
      • Contact: I-Mab PI - 1002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Givastomig Arm 1 Combination; Givastomig (IV) 8 mg/kg every 2 weeks (Q2W) in combination with nivolumab and modified FOLFOX (mFOLFOX) or Givastomig 12 mg/kg every 3 weeks (Q3W) in combination with nivolumab and CAPOX	Drug: Givastomig; Givastomig 8mg/kg Q2W IV or 12mg/kg Q3W IV; Other Names: TJ033721; Drug: Nivolumab; Q2 or Q3W IV; Drug: 5Fluorouracil; Q2W IV; Other Names: 5-FU; Drug: Leucovorin; Q2W IV; Drug: Oxaliplatin; Q2W or Q3W IV; Drug: Capecitabine; Twice daily x 14 days every 3 weeks PO
Experimental: Experimental: Givastomig Arm 2 Combination; Givastomig (IV) 12 mg/kg every 2 weeks (Q2W) in combination with nivolumab and modified FOLFOX (mFOLFOX) or Givastomig 18 mg/kg every 3 weeks (Q3W) in combination with nivolumab and CAPOX	Drug: Givastomig; Givastomig 8mg/kg Q2W IV or 12mg/kg Q3W IV; Other Names: TJ033721; Drug: Nivolumab; Q2 or Q3W IV; Drug: 5Fluorouracil; Q2W IV; Other Names: 5-FU; Drug: Leucovorin; Q2W IV; Drug: Oxaliplatin; Q2W or Q3W IV; Drug: Capecitabine; Twice daily x 14 days every 3 weeks PO
Active Comparator: Control: Nivolumab Plus Chemotherapy; Nivolumab in combination with modified FOLFOX (mFOLFOX) or CAPOX	Drug: Nivolumab; Q2 or Q3W IV; Drug: 5Fluorouracil; Q2W IV; Other Names: 5-FU; Drug: Leucovorin; Q2W IV; Drug: Oxaliplatin; Q2W or Q3W IV; Drug: Capecitabine; Twice daily x 14 days every 3 weeks PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS), BICR-assessed	Compare PFS between participants receiving givastomig plus nivolumab and chemotherapy versus control (nivolumab plus chemotherapy)	Up to 5 years
Safety and Tolerability	Incidence, severity, and type of adverse events, including treatment-emergent and immune-related adverse events, graded by NCI CTCAE v5.0	Throughout treatment and up to 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR), BICR-assessed	Proportion of participants with complete or partial response by RECIST v1.1	Up to 108 weeks
Duration of Response (DOR), BICR-assessed	Time participants maintain complete or partial response	Up to 108 weeks
Best Overall Response (BOR), BICR-assessed	Best response achieved during treatment according to RECIST v1.1	Up to 108 weeks
Overall Survival (OS)	Comparison of overall survival between arms	Up to 5 years
Optimized Dose of Givastomig	Determine the recommended dose of givastomig in combination with nivolumab and chemotherapy	Up to 2 years
Peak Plasma Concentration (Cmax) of Givastomig	Cmax will be derived from the PK plasma samples collected	Up to 2 years
Correlation of baseline CLDN18.2 expression with response and safety measures	Tumor expression of CLDN18.2 will be assessed at baseline and will be correlated with measures of response (including ORR, PFS, OS) and safety (incidence of AEs)	Baseline and up to 2 years
Change in serum levels of soluble 4-1BB (s4-1BB) from baseline	Serum s4-1BB levels will be assessed at baseline and while on treatment. Changes will be correlated with efficacy measures including ORR.	Baseline and up to 2 years
Health Related Quality of Life (HRQoL) measured by the Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)	The EORTC QLQ-C30 is a cancer specific instrument consisting of 5 functional domain scales: physical, role, emotional, social, and cognitive	Baseline and up to 2 years
Trough Plasma Concentration (Ctrough) of Givastomig	Ctrough will be derived from the PK plasma samples collected	Up to 2 years
Number of participants positive for anti-drug antibody (ADA) to Givastomig	Immunogenicity will be measured by the number of participants that are ADA positive	Up to 2 years
Correlation of baseline PDL1 expression with response and safety measures	Tumor expression of PDL1 will be assessed at baseline and will be correlated with measures of response (including ORR, PFS, OS) and safety (incidence of AEs)	Baseline and up to 2 years
HRQoL measured by the Oesophago-Gastric Module (EORTC QLQ-OG25) questionnaire	The EORTC-QLQ-OG25 questionnaire evaluates gastric cancer and gastroesophageal cancer specific symptoms	Baseline and up to 2 years
HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L)	he EQ-5D-5L questionnaire is a validated measure of generic health outcomes including mobility, self-care, usual activities, pain/depression, and anxiety/depression	Baseline and up to 2 years

Collaborators and Investigators

• Sponsor: I-Mab Biopharma US Limited

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Stomach Neoplasms; Neoplasm Metastasis; Adenocarcinoma Of Esophagus; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Capecitabine; Oxaliplatin; Nivolumab; Fluorouracil; Leucovorin
• Other Study ID Numbers: IMAB033721GCA201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No