A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression

NCT06682793 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: A2B395-101
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 10

Brief Summary

The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and other solid tumors that express EGFR and have lost HLA-A\*02 expression. The main questions this study aims to answer are:

• Phase 1: What is the recommended dose of A2B395 that is safe for patients
• Phase 2: Does the recommended dose of A2B395 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 in BASECAMP-1 (NCT04981119)
• Preconditioning lymphodepletion (PCLD) regimen
• A2B395 Tmod CAR T cells at the assigned dose

Conditions

Solid Tumor, Adult; Colorectal Cancer; Non-Small Cell Lung; NSCLC (Non-small Cell Lung Cancer); Cancer; Colon Cancer; Rectal Cancer; Lung Cancer; CRC; Head and Neck Squamous Cell Cancer; HNSCC; Renal Cell Carcinoma; RCC; Kidney Cancer; Triple Negative Breast Cancer; TNBC; Colorectal Adenocarcinoma

Keywords

CAR T Cell; Solid Tumors; Allogeneic; T Cell; EGFR; HLA-A2; Solid tumors expressing EGFR; CRC; Colorectal; Cell Therapy; Gene Therapy; Blocker; Cancer; NSCLC; Non small Cell Lung Cancer; Lung Cancer; renal cell carcinoma; RCC; Kidney Cancer; Renal cell cancer; Triple negative breast cancer; TNBC

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 (CTCAE) version 5.0 (or current version). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and graft versus host disease (GvHD) 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 A2B395 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.

  28 days post A2B395 infusion

• Phase 2: The overall response rate (ORR) for patients

  The ORR will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and assessed by independent central review.

  24 months post A2B395 infusion

Secondary Outcomes (3)

• Persistence of A2B395

  up to 24 months post A2B395 infusion

• Cytokine analysis

  up to 24 months post A2B395 infusion

• Cytokine analysis

  up to 24 months post A2B395 infusion

Study Arms (1)

A2B395

EXPERIMENTAL

Participants receive preconditioning lymphodepletion (PCLD) regimen followed by a single dose of A2B395 intravenously on day 0

Biological: A2B395; Diagnostic Test: xT CDx with HLA-LOH assay

Interventions

A2B395 BIOLOGICAL

Allogeneic logic-gated Tmod CAR T cells

Also known as: Tmod CAR T-cell Therapy

A2B395

xT CDx with HLA-LOH assay DIAGNOSTIC_TEST

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

A2B395

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).
• Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, HNSCC, TNBC, RCC, or other solid tumors with EGFR 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
• Cancer therapy within 3 weeks or 3 half lives of A2B395 infusion
• Radiotherapy within 28 days of A2B395 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 of A2B395

Sponsors & Collaborators

• A2 Biotherapeutics Inc.: lead

Study Sites (10)

Banner MD Anderson Cancer Center

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

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33606, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (5)

• DiAndreth B, Hamburger AE, Xu H, Kamb A. The Tmod cellular logic gate as a solution for tumor-selective immunotherapy. Clin Immunol. 2022 Aug;241:109030. doi: 10.1016/j.clim.2022.109030. Epub 2022 May 11.

  PMID: 35561999 BACKGROUND

• Oh J, Kirsh C, Hsin JP, Radecki KC, Zampieri A, Manry D, Ando Y, Miller S, Chan J, McLeod E, Cunningham KM, Wong LM, Xu H, Kamb A. NOT gated T cells that selectively target EGFR and other widely expressed tumor antigens. iScience. 2024 May 7;27(6):109913. doi: 10.1016/j.isci.2024.109913. eCollection 2024 Jun 21.

  PMID: 38799557 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

• 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

• 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

Related Links

• A2 Biotherapeutics Inc.

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Lung Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Kidney Neoplasms; Triple Negative Breast 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; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Adenocarcinoma; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: May 22, 2025
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2030
• Last Updated: September 9, 2025

Record last verified: 2025-09

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 (10)