A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Participants with Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

Last updated: March 6, 2025
Sponsor: A2 Biotherapeutics Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Colon Cancer

Neoplasms

Vaginal Cancer

Treatment

xT CDx with HLA-LOH Assay

A2B694

Clinical Study ID

NCT06051695
A2B694-101
  • Ages > 18
  • All Genders

Study Summary

The goal of this study is to test A2B694, an autologous logic-gated Tmod™ CAR T-cell product 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 MSLN and have lost HLA-A*02 expression.

The main questions this study aims to answer are:

Phase 1: What is the recommended dose of A2B694 that is safe for patients

Phase 2: Does the recommended dose of A2B694 kill the 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

A2B694 Tmod CAR T cells at the assigned dose

Eligibility Criteria

Inclusion

Inclusion Criteria:

Key Inclusion Criteria:

  1. Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissuedemonstrating LOH of HLA-A*02 by NGS (whenever possible from the primary site),successful apheresis and PBMC processing, and with sufficient stored cells availablefor Tmod CAR T-cell therapy

  2. Histologically confirmed recurrent unresectable, locally advanced, or metastaticCRC, NSCLC, PANC, OVCA, MESO, or other solid tumors with MSLN expression. Measurabledisease is required with lesions of >1.0 cm by CT.

  3. Received previous required therapy for the appropriate solid tumor disease asdescribed 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 safetyfollow up

Exclusion

Key Exclusion Criteria:

  1. Has disease that is suitable for local therapy or able to receive standard of caretherapy 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 A2B694 infusion

  6. Radiotherapy within 28 days of A2B694 infusion

  7. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiacdisease within the last 6 months

  8. Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3months of enrollment. Therapeutic dosing of anticoagulants is allowed for history ofPE or DVT if greater than 3 months from time of enrollment, and adequately treated

  9. History of interstitial lung disease including drug-induced interstitial lungdisease and radiation pneumonitis that requires treatment with prolonged steroids orother 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 topractice birth control from the time of consent through 6 months post infusion ofA2B694

Study Design

Total Participants: 230
Treatment Group(s): 2
Primary Treatment: xT CDx with HLA-LOH Assay
Phase: 1/2
Study Start date:
April 03, 2024
Estimated Completion Date:
June 30, 2029

Study 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-A02 heterozygous, with tumors that express MSLN and have lost HLA-A02 expression. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B694 (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 A2B694.

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 A2B694 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have LOH for HLA-A02 protein). Additionally, normal healthy cells that maintain HLA-A02 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.

Connect with a study center

  • Banner Health

    Gilbert, Arizona 85234
    United States

    Active - Recruiting

  • City of Hope

    Duarte, California 91010
    United States

    Site Not Available

  • UCSD Moores Cancer Center

    La Jolla, California 92093
    United States

    Active - Recruiting

  • UCLA Medical Center

    Los Angeles, California 90404
    United States

    Active - Recruiting

  • Stanford University

    Stanford, California 94305
    United States

    Active - Recruiting

  • Mayo Clinic

    Jacksonville, Florida 32224
    United States

    Active - Recruiting

  • Moffitt Cancer Center

    Tampa, Florida 33606
    United States

    Active - Recruiting

  • Massachusetts General Hopsital/Dana Farber Cancer Center

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • Washington University

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Washington University

    St. Louis, Missouri 63110
    United States

    Active - Recruiting

  • NYU Langone Medical Center

    New York, New York 10016
    United States

    Active - Recruiting

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • Fred Hutchinson Cancer Center

    Seattle, Washington 98109
    United States

    Active - Recruiting

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