Actively Recruiting
CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- 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
308 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
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.
CONDITIONS
Official 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
- Diagnosed with advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the stomach, gastroesophageal junction, or esophagus
- Measurable or evaluable disease according to RECIST 1.1 criteria
- Lesions suitable for research biopsy, unless waived by the principal investigator
- Known HER2 status if adenocarcinoma histology prior to enrollment
- For dose escalation, documented HER2 negative cancer required
- For dose expansion, enrollment into either HER2 positive or negative cohorts
- No prior systemic treatment for unresectable or advanced gastric, GEJ, or esophageal cancer
- Previous neoadjuvant or adjuvant therapy allowed if more than 3 months before study start
- Up to two prior cycles of FOLFOX chemotherapy allowed
- Definitive chemoradiation allowed if last treatment was more than 3 months before study start
- Prior palliative radiation allowed if last treatment was more than 10 days before study start
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate bone marrow and organ function as defined by laboratory criteria
- Creatinine phosphokinase elevation less than Grade 2 at screening
- Stable dose of cholesterol-lowering statin for at least 3 weeks prior to study
- For expansion Cohort B, left ventricular ejection fraction above the lower limit of normal
- Agreement to use adequate contraception during and after study participation
- Ability to understand and sign informed consent
You will not qualify if you...
- Current use or expected need for alternative or botanical cancer treatments (medical marijuana allowed)
- History of other malignancies unless treated and disease-free for at least 2 years or known indolent malignancies not requiring treatment
- History of allogeneic organ or stem cell transplant
- Current treatment with other investigational agents (except imaging tracers with 7-day washout)
- Presence of intraluminal gastrointestinal stents (biliary stents allowed)
- History of significant tumor bleeding requiring transfusion or multiple interventions
- Untreated ulcerating tumors
- Use of systemic anticoagulants or antiplatelet therapies within 5 half-lives before study start
- Use of NSAIDs within 5 half-lives before study start
- Active untreated central nervous system metastases
- Known allergy to study drugs or similar compounds
- Use of drugs that prolong QTc interval 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 screening ECG
- Gastrointestinal conditions impairing drug absorption
- Uncontrolled serious illnesses such as active infection or unstable heart conditions
- Pregnant or breastfeeding women; women of childbearing potential must have negative pregnancy test
- HIV patients with CD4 counts below 350 or recent AIDS-defining infections
- Active or suspected autoimmune diseases requiring systemic immunosuppression
- Use of systemic corticosteroids above 10 mg prednisone equivalent within 14 days of treatment (some exceptions apply)
- Unwillingness to follow lifestyle guidance in the protocol
AI-Screening
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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.
CONTACT
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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