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 (EVEREST-1)

A2 Biotherapeutics

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Solid Tumor

NSCLC, Recurrent

Non Small Cell Lung Cancer Recurrent

Solid Tumor, Adult

Pancreas Cancer

Cancer

Non Small Cell Lung Cancer

Colorectal Cancer Metastatic

CRC

Colorectal Adenocarcinoma

Non-Small Cell Squamous Lung Cancer

Colorectal Neoplasms

Colorectal Cancer

NSCLC

Pancreatic Neoplasms

Pancreatic Cancer

Treatments

Biological: A2B530

Diagnostic Test: xT-Onco with HLA-LOH Assay

Study type

Interventional

Funder types

Industry

Identifiers

NCT05736731

A2B530-101

Details and patient eligibility

About

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

Full description

This is a phase 1/2, multi-center, open-label study that enrolls adult subjects with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, or other solid tumors with CEA expression. Subjects must be germline HLA-A*02 heterozygous, with tumors that express CEA and somatic loss of HLA-A*02. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B530 (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 A2B530.

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 A2B530 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express CEA and have LOH for HLA-A*02 protein). Additionally, normal healthy cells that maintain HLA-A*02 expression and co-express CEA (eg, gut mucosal 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-1) and the participant's T cells are then manufactured and infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-1 based on their own disease course.

Enrollment

160 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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