Phase I Trial of CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer

This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm. Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.

Drug: CA-4948, Biological: Pembrolizumab, Drug: Trastuzumab, Drug: mFOLFOX7