Evaluating a new CAR T-cell therapy for solid tumors expressing MSLN

A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

This study is testing a new CAR T-cell therapy to see if it can safely treat adults with solid tumors like colorectal and lung cancer that express a specific protein.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 474 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: A2 Biotherapeutics Inc. (industry)
• Drugs / interventions: CAR T, radiation
• Locations: 12 sites (Gilbert, Arizona and 11 other locations)
• Trial ID: NCT06051695 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of A2B694, a logic-gated CAR T-cell therapy, in adults with solid tumors such as colorectal cancer, non-small cell lung cancer, and others that express mesothelin and have lost HLA-A*02 expression. The study is divided into two phases: Phase 1 focuses on determining the recommended safe dose of A2B694, while Phase 2 assesses its effectiveness in killing tumor cells while protecting healthy cells. Participants will undergo apheresis for cell collection, followed by a lymphodepletion regimen and administration of the CAR T cells. The goal is to provide a safer and more effective treatment option for patients with advanced solid tumors.

Who should consider this trial

Good fit: Ideal candidates are adults with recurrent unresectable solid tumors expressing mesothelin and having lost HLA-A*02 expression.

Not a fit: Patients with solid tumors that are suitable for local therapy or can receive standard of care treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a novel and less toxic treatment option for patients with advanced solid tumors.

How similar studies have performed: While CAR T-cell therapies have shown success in hematological malignancies, this approach for solid tumors is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

Key Inclusion Criteria:

1. Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A\*02 by NGS (whenever possible from the primary site), successful apheresis and PBMC processing, and with sufficient stored cells available for Tmod CAR T-cell therapy
2. Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, OVCA, MESO, or other solid tumors with MSLN expression. Measurable disease is required with lesions of ≥1.0 cm by CT.
3. Received previous required therapy for the appropriate solid tumor disease as described in the protocol
4. Has adequate organ function as described in the protocol
5. ECOG performance status of 0 to 1
6. Life expectancy of ≥3 months
7. Willing to comply with study schedule of assessments including long term safety follow up

Key Exclusion Criteria:

1. Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative
2. Prior allogeneic stem cell transplant
3. Prior solid organ transplant
4. MESO with pleural involvement extending into the peritoneum
5. Cancer therapy within 3 weeks or 3 half lives of infusion
6. Radiotherapy within 28 days of infusion
7. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months
8. Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3 months of enrollment. Therapeutic dosing of anticoagulants is allowed for history of PE or DVT if greater than 3 months from time of enrollment, and adequately treated
9. History of interstitial lung disease including drug-induced interstitial lung disease and radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year
10. Requires supplemental home oxygen
11. Females of childbearing potential who are pregnant or breastfeeding
12. Subjects, both male and female, of childbearing potential who are not willing to practice birth control from the time of consent through 6 months post infusion

Where this trial is running

Gilbert, Arizona and 11 other locations

• Banner Health — Gilbert, Arizona, United States (RECRUITING)
• UCSD Moores Cancer Center — La Jolla, California, United States (RECRUITING)
• UCLA Medical Center — Los Angeles, California, United States (RECRUITING)
• Stanford University — Stanford, California, United States (RECRUITING)
• Mayo Clinic — Jacksonville, Florida, United States (RECRUITING)
• Moffitt Cancer Center — Tampa, Florida, United States (RECRUITING)
• Mayo Clinic Rochester — Rochester, Minnesota, United States (RECRUITING)
• Washington University — St Louis, Missouri, United States (RECRUITING)
• NYU Langone Medical Center — New York, New York, United States (RECRUITING)
• The Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (RECRUITING)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (RECRUITING)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (RECRUITING)

Study contacts

• Study coordinator: Clinical Trials

Conditions: Solid Tumor, Adult, Colorectal Cancer, NSCLC, Non Small Cell Lung Cancer, NSCLC, Recurrent, Non-Small Cell Squamous Lung Cancer, Pancreas Cancer, Pancreatic Neoplasm