Trial Title:
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
NCT ID:
NCT05736731
Condition:
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
Conditions: Official terms:
Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Pancreatic Neoplasms
Recurrence
Conditions: 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
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
A2B530
Description:
Autologous logic-gated Tmod CAR T-cells
Arm group label:
A2530
Other name:
Tmod CAR T-cell Therapy
Intervention type:
Diagnostic Test
Intervention name:
xT-Onco with HLA-LOH Assay
Description:
An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical
device
Arm group label:
A2530
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
Detailed 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.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. 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
2. 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).
3. Received previous required therapy for the appropriate solid tumor disease as
described in the protocol
4. Has adequate organ function as described in the protocol
5. ECOG performance status of 0 to 1
6. Life expectancy of ≥3 months
7. Willing to comply with study schedule of assessments including long term safety
follow up
Key Exclusion Criteria:
1. Has disease that is suitable for local therapy or able to receive standard of care
therapy that is therapeutic and not palliative
2. Prior allogeneic stem cell transplant
3. Prior solid organ transplant
4. Cancer therapy within 3 weeks or 3 half lives of A2B530 infusion
5. Radiotherapy within 28 days of A2B530 infusion
6. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac
disease within the last 6 months
7. 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.
8. Requires supplemental home oxygen
9. Females of childbearing potential who are pregnant or breastfeeding
10. 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Banner Health
Address:
City:
Gilbert
Zip:
85234
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Ulrickson, MD
Contact backup:
Last name:
Yasmin Adam
Email:
yasmin.adam2@bannerhealth.com
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
90101
Country:
United States
Status:
Withdrawn
Facility:
Name:
University of California San Diego
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sandip Patel, MD
Contact backup:
Last name:
Jona Plevin
Phone:
8582463253
Email:
jplevin@health.ucsd.edu
Facility:
Name:
UCLA Medical Center
Address:
City:
Los Angeles
Zip:
90404
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christopher Hannigan
Email:
channigan@mednet.ucla.edu
Contact backup:
Last name:
J. Randolph Hecht, MD
Facility:
Name:
Stanford University
Address:
City:
Stanford
Zip:
94305
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vivian Leung
Email:
vivian0@stanford.edu
Contact backup:
Last name:
Wen-Kai Weng, MD, PhD
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rebecca Delph
Email:
Rebecca.Delph@moffitt.org
Contact backup:
Last name:
Kedar Kirtane
Facility:
Name:
Mayo Clinic Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mohammed Elhaj
Email:
elhaj.mohammed@mayo.edu
Contact backup:
Last name:
Julian Molina, MD, PhD
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amberly Scott
Email:
amberly@wustl.edu
Contact backup:
Last name:
Patrick Grierson, MD PhD
Facility:
Name:
NYU Langone Medical Center
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Contact:
Last name:
Salman Punekar, MD
Phone:
212 731 6228
Email:
Salman.Punekar@nyulangone.org
Contact backup:
Last name:
Maria Herrmann
Email:
maria.herrmann@nyulangone.org
Contact backup:
Last name:
Salman Punekar, MD
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
GI Clinical Trials
Email:
GIClinicalTrials@mdanderson.org
Contact backup:
Last name:
Maria Pia Morelli, MD, PhD
Start date:
April 28, 2023
Completion date:
December 2028
Lead sponsor:
Agency:
A2 Biotherapeutics Inc.
Agency class:
Industry
Collaborator:
Agency:
Tempus AI
Agency class:
Industry
Source:
A2 Biotherapeutics Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05736731
http://www.a2bio.com
https://clinicaltrials.gov/ct2/show/NCT04981119?term=LOH+Apheresis&cond=Cancer&cntry=US&draw=2&rank=1
