Washington University School of Medicine
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.
Inclusion Criteria: * Advanced unresectable or metastatic histologically or cytologically confirmed adenocarcinoma or squamous cell carcinoma of the stomach, gastroesophageal junction, or esophagus * Measurable or evaluable disease defined by RECIST 1.1. * Lesions amenable to research biopsy. This criteria can be waived by the PI after documented discussion with the treating physician. * Known HER2 status if histology is adenocarcinoma prior to enrollment; results from local CLIA laboratory is acceptable. * For Dose Escalation, patients are required to have documented HER2 negative cancer.…
Provided by Curis, Inc.
240 mg IV on Day 1 of each cycle
400 mg IV on Day 1 of every 3 cycles (C1D1, C4D1, C7D1,…) and dosing may continue for a max of 2 years
6 mg/kg IV loading dose on Cycle 1 Day 1 and 4 mg/kg IV on Day 1 of every subsequent cycle
Standard of care