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
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).
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.
Parallel
Givastomig
DrugGivastomig 8mg/kg Q2W IV or 12mg/kg Q3W IV
Nivolumab
DrugQ2 or Q3W IV
5Fluorouracil
DrugQ2W IV
Leucovorin
DrugQ2W IV
Oxaliplatin
DrugQ2W or Q3W IV
Capecitabine
DrugTwice daily x 14 days every 3 weeks PO
Progression-Free Survival (PFS), BICR-assessed
Compare PFS between participants receiving givastomig plus nivolumab and chemotherapy versus control (nivolumab plus chemotherapy)
Safety and Tolerability
Incidence, severity, and type of adverse events, including treatment-emergent and immune-related adverse events, graded by NCI CTCAE v5.0
Objective Response Rate (ORR), BICR-assessed
Proportion of participants with complete or partial response by RECIST v1.1
Duration of Response (DOR), BICR-assessed
Time participants maintain complete or partial response
Best Overall Response (BOR), BICR-assessed
Best response achieved during treatment according to RECIST v1.1
Overall Survival (OS)
Comparison of overall survival between arms
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