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

Summary

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.

Eligibility

Age range

18+ years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  CA-4948

  Provided by Curis, Inc.

• Biological
  Nivolumab

  240 mg IV on Day 1 of each cycle

• Biological
  Pembrolizumab

  400 mg IV on Day 1 of every 3 cycles (C1D1, C4D1, C7D1,…) and dosing may continue for a max of 2 years

• Drug
  Trastuzumab

  6 mg/kg IV loading dose on Cycle 1 Day 1 and 4 mg/kg IV on Day 1 of every subsequent cycle

• Drug
  mFOLFOX7

  Standard of care

Location