Actively Recruiting
Phase I Trial of CA-4948 Combined With FOLFOX and PD-1 Inhibitors With or Without Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer
Led by Washington University School of Medicine · Updated on 2026-04-27
42
Participants Needed
1
Research Sites
39 weeks
Total Duration
On this page
Sponsors
W
Washington University School of Medicine
Lead Sponsor
C
Curis, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and dosing of CA-4948 combined with FOLFOX chemotherapy and PD-1 inhibitors, with or without trastuzumab, in adults with untreated, unresectable gastric, gastroesophageal junction, or esophageal cancer. This phase I trial aims to find the best dose of CA-4948 in combination with these treatments and to assess their safety in patients with HER2 positive or negative cancers. The study includes a Dose Escalation phase where different doses of CA-4948 are tested with FOLFOX and nivolumab to determine the recommended dose. Dose Expansion follows with two groups: Cohort A receives CA-4948, FOLFOX, and nivolumab for HER2 negative patients, while Cohort B receives CA-4948 with FOLFOX, pembrolizumab, and trastuzumab for HER2 positive patients. Treatments are given in 14-day cycles, with CA-4948 taken orally twice daily and other drugs administered intravenously according to schedule. Participants will be monitored for safety through tracking adverse events up to 30 days after treatment completion, which is estimated to take about 15 months. Researchers will measure treatment responses, progression-free survival, overall survival, and other outcomes over time. Study visits include drug administration, laboratory tests, imaging, and biopsies when possible. The total study duration varies by participant, with close follow-up to evaluate treatment effects and safety.
CONDITIONS
Brief Title
CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histologically or cytologically confirmed unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the stomach, gastroesophageal junction, or esophagus
- Measurable or evaluable disease by RECIST 1.1
- Lesions suitable for research biopsy (may be waived by principal investigator)
- Known HER2 status if adenocarcinoma; HER2 negative required for dose escalation; HER2 positive or negative allowed for dose expansion
- No prior systemic treatment for unresectable or advanced gastric, GEJ, or esophageal cancer, except neoadjuvant/adjuvant therapy completed over 3 months ago
- Up to two prior cycles of FOLFOX allowed
- Prior chemoradiation allowed if last treatment was over 3 months ago
- Prior palliative radiation allowed if last treatment was over 10 days ago
- ECOG performance status 0 or 1
- Adequate bone marrow and organ function as defined by lab criteria
- Creatinine phosphokinase below grade 2
- Stable dose of cholesterol-lowering statins for at least 3 weeks prior
- For expansion cohort B: left ventricular ejection fraction above lower limit of normal
- Willingness to use adequate contraception if of childbearing potential
- Ability to provide informed consent
You will not qualify if you...
- Use of alternative or holistic cancer treatments, except medical marijuana
- History of other malignancies unless treated over 2 years ago and no evidence of disease or indolent malignancies not requiring treatment
- History of allogeneic organ or stem cell transplant
- Use of other investigational therapies, except imaging tracers with 7-day washout
- Presence of intraluminal gastrointestinal stents (except biliary)
- History of significant tumor bleeding requiring transfusions or multiple interventions
- Untreated ulcerating tumor unless treated and assessed eligible
- Use of systemic anticoagulants, anti-platelet agents, or NSAIDs within 5 half-lives before treatment
- Active brain metastases; treated and stable allowed at discretion
- Allergic reactions to study drugs or similar compounds
- Use of drugs causing prolonged QTc or history of related arrhythmias
- Interstitial lung disease or pneumonitis grade 2 or higher
- Live attenuated vaccine within 30 days prior to enrollment
- QTc interval over 470 ms on EKG
- Gastrointestinal conditions impairing drug absorption or inability to swallow CA-4948
- Uncontrolled illness including infection, heart failure, unstable angina, or arrhythmia
- Pregnant or breastfeeding women; negative pregnancy test required
- HIV patients with low CD4 counts or recent AIDS-defining infections
- Active or suspected autoimmune disease except certain controlled conditions
- Use of systemic immunosuppressive medications or corticosteroids above specified doses within 14 days
- Unwillingness to follow study lifestyle guidance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 14-day cycles up to approximately 15 months or until discontinuation
Participants receive CA-4948 twice daily by mouth combined with standard of care mFOLFOX7 chemotherapy every 14 days, along with either Nivolumab every 14 days or Pembrolizumab every 3 cycles plus Trastuzumab every 14 days depending on cohort assignment.
Every 14 days for infusions; daily oral medication
Duration - Up to 30 days post treatment completion
Participants are monitored for safety and disease progression after completing treatment.
Approximately 1 to 2 visits
Trial Site Locations
Total: 1 location
1
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
Research Team
P
Patrick Grierson, M.D., Ph.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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