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

NCT07432295 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IMAB033721GCA201
• Study Type: interventional
• Target: 180
• Locations: 3 countries
• Sites: 6

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• Objective Response Rate (ORR), BICR-assessed

  Up to 108 weeks

• Duration of Response (DOR), BICR-assessed

  Up to 108 weeks

• Best Overall Response (BOR), BICR-assessed

  Up to 108 weeks

• Overall Survival (OS)

  Up to 5 years

• Optimized Dose of Givastomig

  Up to 2 years

Study Arms (3)

Experimental: Givastomig Arm 1 Combination

EXPERIMENTAL

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; Drug: Nivolumab; Drug: 5Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Experimental: Givastomig Arm 2 Combination

EXPERIMENTAL

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; Drug: Nivolumab; Drug: 5Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Control: Nivolumab Plus Chemotherapy

ACTIVE COMPARATOR

Nivolumab in combination with modified FOLFOX (mFOLFOX) or CAPOX

Drug: Nivolumab; Drug: 5Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Givastomig DRUG

Givastomig 8mg/kg Q2W IV or 12mg/kg Q3W IV

Also known as: TJ033721

Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

Nivolumab DRUG

Q2 or Q3W IV

Control: Nivolumab Plus Chemotherapy; Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

5Fluorouracil DRUG

Q2W IV

Also known as: 5-FU

Control: Nivolumab Plus Chemotherapy; Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

Leucovorin DRUG

Q2W IV

Control: Nivolumab Plus Chemotherapy; Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

Oxaliplatin DRUG

Q2W or Q3W IV

Control: Nivolumab Plus Chemotherapy; Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

Capecitabine DRUG

Twice daily x 14 days every 3 weeks PO

Control: Nivolumab Plus Chemotherapy; Experimental: Givastomig Arm 1 Combination; Experimental: Givastomig Arm 2 Combination

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• I-Mab Biopharma US Limited: lead

Study Sites (6)

I-Mab Site 1016

Goodyear, Arizona, 85338, United States

RECRUITING

I-MAB Site 1005

Duarte, California, 91010, United States

RECRUITING

I-Mab Site 1002

Boston, Massachusetts, 02114, United States

RECRUITING

I-Mab Site 2001

Beijing, China

RECRUITING

I-Mab Site - 4001

Kashiwa, Japan

NOT YET RECRUITING

I-Mab Site 4005

Tokyo, Japan

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Stomach Neoplasms; Adenocarcinoma Of Esophagus

Interventions

Nivolumab; Fluorouracil; Leucovorin; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

I-MAB US Clinical Trials

CONTACT

301-294-4408; us.info@imabbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 25, 2026
• Study Start: February 11, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); JP (2); US (3)