A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Participants With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression

NCT05736731 | Active Not Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: A2B530-101
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 8

Brief Summary

The goal of this study is to test A2B530,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), and other solid tumors that express CEA and have lost HLA-A\*02 expression. The main questions this study aims to answer are:

• Phase 1: What is the maximum or recommended dose of A2B530 that is safe for patients
• Phase 2: Does the recommended dose of A2B530 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
• A2B530 Tmod CAR T cells at the assigned dose

Conditions

Solid Tumor, Adult; Solid Tumor; Pancreatic Cancer; Pancreatic Neoplasms; Pancreas Cancer; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Recurrent; Non-Small Cell Squamous Lung Cancer; NSCLC; NSCLC, Recurrent; Colorectal Cancer; Colorectal Neoplasms; Colorectal Adenocarcinoma; CRC; Colorectal Cancer Metastatic; Cancer

Keywords

CAR T Cell; Solid Tumors; autologous; T cell; Carcinoembryonic Antigen; CEA; HLA-A2; Solid Tumors Expressing CEA; Pancreatic Cancer; PANC; CRC; Colorectal Cancer; NSCLC; Non-Small Cell Lung Cancer

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 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 A2B530 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 A2B530 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 A2B530 infusion

Secondary Outcomes (2)

• Persistence of A2B530

  up to 24 months post A2B530 infusion

• Cytokine analysis

  up to 24 months post A2B530 infusion

Study Arms (1)

A2530

EXPERIMENTAL

Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B530 intravenously on day 0

Biological: A2B530; Diagnostic Test: xT-Onco with HLA-LOH Assay

Interventions

A2B530 BIOLOGICAL

Autologous logic-gated Tmod CAR T-cells

Also known as: Tmod CAR T-cell Therapy

A2530

xT-Onco with HLA-LOH Assay DIAGNOSTIC_TEST

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

A2530

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\*02:01 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, or other solid tumors associated with CEA expression. Measurable disease is required with lesions of \>1.0 cm by computed tomography (CT). (Soluble CEA is not acceptable as the sole measure of disease).
• 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 A2B530 infusion
• Radiotherapy within 28 days of A2B530 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.
• 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 A2B530

Sponsors & Collaborators

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

Study Sites (8)

Banner Health

Gilbert, Arizona, 85234, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

UCLA Medical Center

Los Angeles, California, 90404, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33136, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (5)

• 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

• Perera J, Mapes B, Lau D, et al. Detection of human leukocyte antigen class I loss of heterozygosity in solid tumor types by next-generation DNA sequencing. J Immunother Cancer. 2019, 7(Suppl 1):P103

  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

• Sandberg ML, Wang X, Martin AD, Nampe DP, Gabrelow GB, Li CZ, McElvain ME, Lee WH, Shafaattalab S, Martire S, Fisher FA, Ando Y, Liu E, Ju D, Wong LM, Xu H, Kamb A. A carcinoembryonic antigen-specific cell therapy selectively targets tumor cells with HLA loss of heterozygosity in vitro and in vivo. Sci Transl Med. 2022 Mar 2;14(634):eabm0306. doi: 10.1126/scitranslmed.abm0306. Epub 2022 Mar 2.

  PMID: 35235342 BACKGROUND

Related Links

• A2 Biotherapeutics Inc.
• BASECAMP-1 Study

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence; Colorectal Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Eric Ng, MD

  A2 Biotherapeutics Inc.

  STUDY DIRECTOR

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: January 30, 2023
• First Posted: February 21, 2023
• Study Start: April 28, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

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 (8)