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

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

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.

Arms & interventions

• DrugGivastomig

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

• DrugNivolumab

  Q2 or Q3W IV

• Drug5Fluorouracil

  Q2W IV

• DrugLeucovorin

  Q2W IV

• DrugOxaliplatin

  Q2W or Q3W IV

• DrugCapecitabine

  Twice daily x 14 days every 3 weeks PO

Outcome measures

Eligibility criteria