An official website of the United States government
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
Trial Status: closed to accrual
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
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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05736731.
Locations matching your search criteria
United States
California
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Approved
Name Not Available
Florida
Jacksonville
Mayo Clinic in Florida
Status: Temporarily closed to accrual
Name Not Available
Minnesota
Rochester
Mayo Clinic in Rochester
Status: Temporarily closed to accrual
Name Not Available
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.
