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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The goal of this study is to test autologous logic-gated Tmod™ CAR T-cell products in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express mesothelin (MSLN) and have lost HLA-A\*02 expression. The main questions this study aims to answer are: Phase 1: What is the recommended dose that is safe for patients Phase 2: Does the recommended dose kill solid tumor cells and protect the patient's healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: Enrollment and Apheresis in BASECAMP-1 (NCT04981119) Preconditioning Lymphodepletion (PCLD) Regimen Tmod CAR T cells at the assigned dose

Who May Be Eligible (Plain English)

Who May Qualify: Key Who May Qualify: 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. diagnosed by tissue sample (biopsy-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 your organs (liver, kidneys, etc.) are working well enough based on blood tests as described in the protocol 5. You should be able to carry out daily activities with 0 level of ability (ECOG 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 Who Should NOT Join This Trial: 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

BIOLOGICAL

A2B694

Autologous logic-gated Tmod CAR T cells

BIOLOGICAL

A2B543

Autologous logic-gated Tmod CAR T cells

DIAGNOSTIC_TEST

xT CDx with HLA-LOH Assay

An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device

Locations (12)

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