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NCT06051695 | RECRUITING | Solid Tumor, Adult

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
Sponsor:

A2 Biotherapeutics Inc.

Brief Summary:

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

Condition or disease

Solid Tumor, Adult

Colorectal Cancer

NSCLC

Non Small Cell Lung Cancer

NSCLC, Recurrent

Non-Small Cell Squamous Lung Cancer

Pancreas Cancer

Pancreatic Neoplasm

Colorectal Adenocarcinoma

CRC

Colon Cancer

Rectal Cancer

Cancer

Ovarian Cancer

Ovarian Neoplasms

Mesothelioma

Mesothelioma, Malignant

Ovary Cancer

Lung Cancer

MEAT

Intervention/treatment

A2B694

A2B543

xT CDx with HLA-LOH Assay

Phase

PHASE1

PHASE2

Detailed Description:

This is a seamless phase 1/2, multi-center, open-label study that enrolls adults with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, OVCA, MESO or other solid tumors with MSLN expression. Subjects must be germline HLA-A\*02 heterozygous, with tumors that express MSLN and have lost HLA-A\*02 expression. This study has two arms: Arm 1 is a study of A2B694 and Arm 2 is a study of A2B543. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of the Tmod products (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of the Tmod products. The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have loss of heterozygosity \[LOH\] for HLA-A\*02 protein). Additionally, normal healthy cells that maintain HLA-A\*02 expression and co-express MSLN (eg, lung tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study. Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-2) and the participant's T cells are manufactured and then infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course.

Study Type : INTERVENTIONAL
Estimated Enrollment : 474 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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
Actual Study Start Date : 2024-04-03
Estimated Primary Completion Date : 2028-06
Estimated Study Completion Date : 2029-06

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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
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

Location Details

NCT06051695

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Arizona

Banner Health

Gilbert, arizona, United States, 85234

RECRUITING

United States, California

UCSD Moores Cancer Center

La Jolla, California, United States, 92093

RECRUITING

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90404

RECRUITING

United States, California

Stanford University

Stanford, California, United States, 94305

RECRUITING

United States, Florida

Mayo Clinic

Jacksonville, florida, United States, 32224

RECRUITING

United States, Florida

Moffitt Cancer Center

Tampa, florida, United States, 33606

RECRUITING

United States, Minnesota

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55905

RECRUITING

United States, Missouri

Washington University

St Louis, Missouri, United States, 63110

RECRUITING

United States, New York

NYU Langone Medical Center

New York, New York, United States, 10016

RECRUITING

United States, Ohio

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

RECRUITING

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

RECRUITING

United States, Washington

Fred Hutchinson Cancer Center

Seattle, Washington, United States, 98109