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

NCT05187182 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202202027
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Cancer; Stomach Cancer; Esophagus Cancer; Gastroesophageal Junction Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Safety of regimen as measured by number of adverse events

  From start of treatment through 30 days after completion of treatment (estimated to be 15 months)

• Expansion dose of CA-4948 in combination with FOLFOX/PD-1 inhibitor with/without trastuzumab

  Completion of 2 cycles (each cycle is 14 days) for all participants enrolled in Dose Escalation portion of the study (estimated to be 19 months)

Secondary Outcomes (6)

• Progression-free rate (PFR)

  At 6 months

• Disease control rate (DCR)

  At 6 months post study completion (estimated to be 20 months)

• Overall response rate (ORR) per RECIST 1.1

  Through completion of treatment (estimated to be 14 months)

• Overall response rate (ORR) per iRECIST

  Through completion of treatment (estimated to be 14 months)

• Progression-free survival (PFS)

  At 1 year

Study Arms (3)

Dose Escalation (CA4948 + FOLFOX + Nivolumab)

EXPERIMENTAL

* CA4948 (dose will depend on dose level assigned) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days. * Each cycle is 14 days.

Drug: CA-4948; Biological: Nivolumab; Drug: mFOLFOX7

Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab)

EXPERIMENTAL

* CA4948 (dose will be the recommended phase II dose found in the dose escalation portion of study) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days. * Each cycle is 14 days.

Drug: CA-4948; Biological: Nivolumab; Drug: mFOLFOX7

Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)

EXPERIMENTAL

* CA4948 (dose will be the recommended dose found in the dose escalation portion of study) twice daily by mouth Standard of care mFOLFOX7 every 14 days. Pembrolizumab on day 1 of every 3 cycles. Trastuzumab every 14 days. * Each cycle is 14 days.

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

Interventions

CA-4948 DRUG

Provided by Curis, Inc.

Dose Escalation (CA4948 + FOLFOX + Nivolumab); Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab); Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)

Nivolumab BIOLOGICAL

240 mg IV on Day 1 of each cycle

Also known as: Opdivo

Dose Escalation (CA4948 + FOLFOX + Nivolumab); Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab)

Pembrolizumab BIOLOGICAL

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

Also known as: Keytruda

Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)

Trastuzumab DRUG

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

Also known as: Herceptin

Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)

mFOLFOX7 DRUG

Standard of care

Dose Escalation (CA4948 + FOLFOX + Nivolumab); Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab); Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For Dose Expansion, patients will be enrolled to either HER2 positive or negative cohorts at the time of enrollment
• No prior systemic treatment for unresectable/advanced gastric, GEJ, or esophageal cancer.
• Neoadjuvant or adjuvant systemic therapy is allowed; however, surgical resection and adjuvant chemotherapy should have been \> 3 months from planned C1D1.
• Up to two prior cycles of FOLFOX is allowed.
• Definitive chemoradiation is allowed if the last date of chemotherapy or radiation (whichever is more recent) is \> 3 months from planned C1D1.
• Prior palliative radiation therapy, including brain radiation, in the unresectable setting is allowed, but the last treatment date should be \>10 days from planned C1D1.
• At least 18 years of age
• ECOG performance status 0 or 1
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm

You may not qualify if:

• Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment. Use of medical marijuana is permitted.
• A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of metastatic gastric, GEJ, or esophageal cancer.
• History of allogeneic organ or stem cell transplant
• Currently receiving any other investigational therapeutic agents. Investigational tracers related to imaging studies are allowed with a 7 day-washout.
• Currently have an intraluminal GI stent (gastric, esophageal, small bowel, colon). Biliary stents are allowed.
• History of clinically relevant bleeding from their tumor(s). Includes but is not limited to bleeding tumor requiring RBC transfusion, or bleeding requiring more than one endoscopic intervention.
• Untreated ulcerating tumor. Patients who are endoscopically treated must be assessed by the study PI or delegate for eligibility.
• Use of systemic therapeutic anticoagulation, including daily baby aspirin, within 5 half-lives of the anticoagulant prior to C1D1. Patients can receive heparin or alteplase flush in their ports.
• Use of anti-platelet therapies (i.e. P2Y12 inhibitors (clopidogrel, prasugrel, etc.), within 5 half-lives of the anti-platelet therapy prior to C1D1.
• Use of NSAIDs within 5 half-lives of the NSAID prior to C1D1.
• Clinically active CNS metastasis; treated and asymptomatic metastasis allowed at the discretion of the PI. Radiotherapy to the brain must be completed \> 10 days prior to planned C1D1.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948, FOLFOX, nivolumab, trastuzumab or other agents used in the study.
• Concomitant use of drugs with a known risk of causing prolonged QTc and/or Torsades de Pointes or a history of risk factors for Torsades de Pointes.
• Presence of interstitial lung disease or pneumonitis ≥ G2
• Administration of a live attenuated vaccine within 30 days prior to enrollment.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Curis, Inc.: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Interventions

CA-4948; Nivolumab; pembrolizumab; Trastuzumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Grierson, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Grierson, M.D., Ph.D.

CONTACT

314-747-7689; grierson@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The dose escalation phase will occur first. In the dose expansion phase, participants will be assigned to either Cohort A or Cohort B and treated in parallel.

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: January 11, 2022
• Study Start: June 2, 2023
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)