Pumitamig plus Combination Therapy Versus Nivolumab plus Combination Therapy in Previously Untreated Advanced or Metastatic Gastric, GEJ, or Esophageal Adenocarcinoma

The primary objective of this study is to evaluate the clinical efficacy and optimal dose response of pumitamig in combination with chemotherapy compared to two different dose levels for the management of previously untreated advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma. In a subsequent stage, the selected dose will be compared against nivolumab combined with chemotherapy to assess superior control of tumor growth. Secondary objectives include:

• Comparison of overall survival between the pumitamig combination and the standard treatment.
• Assessment of safety and tolerability profiles.
• Evaluation of patient quality of life.

The study involves a total of 506 patients diagnosed with previously untreated advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The study population includes both males and females within the specified age ranges. Participants are required to have histologically or cytologically confirmed disease with PD-L1 expression of ≥ 1. Selection is restricted to individuals with HER2-negative cancer and measurable disease as defined by RECIST v1.1. The sponsor did not provide information regarding general health status, lifestyle considerations, or specific selection methodologies.

This Phase 2/3, blinded, randomized study evaluates the efficacy and safety of pumitamig in combination with chemotherapy compared to nivolumab combined with chemotherapy. The investigation is conducted in two stages for participants with previously untreated advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma. In the initial phase, two different doses of pumitamig are compared to determine the optimal dosage based on objective response rate and safety profiles. The subsequent phase compares the selected dose against the current standard of care to assess progression-free survival and overall survival. The study includes a screening period to confirm histological diagnosis, PD-L1 expression, HER2-negative status, and measurable disease via RECIST v1.1. Participants will undergo regular follow-up assessments to monitor tumor response and survival outcomes. The trial is estimated to conclude by September 2032.

Pumitamig is administered as a concentrate for solution for infusion via intravenous infusion at concentrations of either 20 mg/ml or 50 mg/ml.

Capecitabine is administered for oral use.

Fluorouracil is administered as a solution for injection.

Oxaliplatin is administered as a solution for infusion.

Calcium folinate is administered as a solution for injection.

Nivolumab is utilized as a comparator treatment in the form of a solution for infusion via intravenous use at a concentration of 10 mg/ml.

The efficacy assessment for this study in participants with adenocarcinoma of the gastric, gastroesophageal junction, or esophageal regions is divided into two phases. In Phase 2, the primary endpoint is the objective response rate to compare the impact of two different doses on tumor growth for dose selection. Secondary endpoints for Phase 2 include progression-free survival, duration of response, time to response, and disease control, all evaluated via RECIST v1.1 through investigator assessment. The recommended dose of pumitamig for Phase 3 will also be determined during this stage.

In Phase 3, the primary efficacy endpoints are progression-free survival and overall survival. Progression-free survival is assessed using radiographic imaging, such as CT scans, via blinded independent central review. Secondary endpoints for Phase 3 include objective response and duration of response, both measured by RECIST v1.1 through the same independent central review process.