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

NCT06051695 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: A2B694-101
• Study Type: interventional
• Target: 474
• Locations: 1 country
• Sites: 12

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

Conditions

Non Small Cell Lung Cancer; Non-Small Cell Squamous Lung Cancer; Pancreas Cancer; Pancreatic Neoplasm; Colorectal Adenocarcinoma; CRC; Colon Cancer; Rectal Cancer; Cancer; Lung Cancer; Solid Tumor, Adult; Colorectal Cancer; NSCLC; NSCLC, Recurrent; Ovarian Cancer; Ovarian Neoplasms; Mesothelioma; Mesothelioma, Malignant; Ovary Cancer; MESOM

Keywords

CAR T Cell; Solid Tumors; Autologous; T Cell; Mesothelin; MSLN; HLA-A2; Solid Tumors expressing MSLN; Pancreatic; Cell Therapy; Gene Therapy; blocker; Cancer; PANC; CRC; Colorectal Cancer; Lung Cancer; NSCLC; OVCA; MESOM; Ovarian Cancer; Mesothelioma; Logic-gate

Outcome Measures

Primary Outcomes (3)

• Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level

  Adverse Events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version (CTCAE) 5.0 (or current version). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events will be graded according to the criteria described in the current protocol.

  From the time of Informed consent until 24 months (2 years) post infusion

• Phase 1: Recommended Phase 2 Dose (RP2D)

  The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.

  21 days post infusion

• Phase 2: The Overall Response Rate (ORR) for patients

  The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.

  24 months post infusion

Secondary Outcomes (2)

• Persistence of Tmod product

  up to 24 months post infusion

• Cytokine analysis

  up to 24 months post infusion

Study Arms (2)

Arm 1: A2B694

EXPERIMENTAL

Patients receive preconditioning lymphodepletion (PCLD) regimen followed by a single dose of A2B694 intravenously on day 0

Biological: A2B694; Diagnostic Test: xT CDx with HLA-LOH Assay

Arm 2: A2B543

EXPERIMENTAL

Patients receive preconditioning lymphodepletion (PCLD) regimen followed by a single dose of A2B543 intravenously on day 0

Biological: A2B543; Diagnostic Test: xT CDx with HLA-LOH Assay

Interventions

A2B694 BIOLOGICAL

Autologous logic-gated Tmod CAR T cells

Also known as: Tmod CAR T-cell Therapy

Arm 1: A2B694

A2B543 BIOLOGICAL

Autologous logic-gated Tmod CAR T cells

Also known as: Tmod CAR T-cell Therapy

Arm 2: A2B543

xT CDx with HLA-LOH Assay DIAGNOSTIC_TEST

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

Arm 1: A2B694; Arm 2: A2B543

Eligibility Criteria

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

You may qualify if:

• 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
• 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.
• Received previous required therapy for the appropriate solid tumor disease as described in the protocol
• Has adequate organ function as described in the protocol
• ECOG performance status of 0 to 1
• Life expectancy of ≥3 months
• Willing to comply with study schedule of assessments including long term safety follow up

You may not qualify if:

• Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative
• Prior allogeneic stem cell transplant
• Prior solid organ transplant
• MESO with pleural involvement extending into the peritoneum
• Cancer therapy within 3 weeks or 3 half lives of infusion
• Radiotherapy within 28 days of infusion
• Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months
• 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
• 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
• Requires supplemental home oxygen
• Females of childbearing potential who are pregnant or breastfeeding
• 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

Sponsors & Collaborators

• A2 Biotherapeutics Inc.: lead
• Tempus AI: collaborator

Study Sites (12)

Banner Health

Gilbert, Arizona, 85234, United States

RECRUITING

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

UCLA Medical Center

Los Angeles, California, 90404, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33606, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Medical Center

New York, New York, 10016, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (4)

• Hamburger AE, DiAndreth B, Cui J, Daris ME, Munguia ML, Deshmukh K, Mock JY, Asuelime GE, Lim ED, Kreke MR, Tokatlian T, Kamb A. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol. 2020 Dec;128:298-310. doi: 10.1016/j.molimm.2020.09.012. Epub 2020 Oct 1.

  PMID: 33012527 BACKGROUND

• Hwang MS, Mog BJ, Douglass J, Pearlman AH, Hsiue EH, Paul S, DiNapoli SR, Konig MF, Pardoll DM, Gabelli SB, Bettegowda C, Papadopoulos N, Vogelstein B, Zhou S, Kinzler KW. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):e2022410118. doi: 10.1073/pnas.2022410118.

  PMID: 33731480 BACKGROUND

• Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.

  PMID: 20164920 BACKGROUND

• Tokatlian T, Asuelime GE, Mock JY, DiAndreth B, Sharma S, Toledo Warshaviak D, Daris ME, Bolanos K, Luna BL, Naradikian MS, Deshmukh K, Hamburger AE, Kamb A. Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells. J Immunother Cancer. 2022 Jan;10(1):e003826. doi: 10.1136/jitc-2021-003826.

  PMID: 35091455 BACKGROUND

Related Links

• A2 Biotherapeutics Inc.

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence; Pancreatic Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Neoplasms; Ovarian Neoplasms; Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Pleural Neoplasms

Study Officials

• John Welch, MD, PhD

  A2 Biotherapeutics

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials

CONTACT

310-431-9180; ClinicalTrials@a2bio.com

Study Design

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

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: September 25, 2023
• Study Start: April 3, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: February 20, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Data will be available within 1 year of the completion of the study, the length of time of availability is to be determined.

Locations

US (12)