Ignite Creation Date:
2025-12-24 @ 1:41 PM
Ignite Modification Date:
2026-01-01 @ 1:49 PM
Study NCT ID:
NCT06051695
Status:
RECRUITING
Last Update Posted:
2025-12-12
First Post:
2023-09-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
Sponsor:
A2 Biotherapeutics Inc.
Organization:
Study Overview
Official Title:
A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EVEREST-2
Brief Summary:
The goal of this study is to test autologous logic-gated Tmod™ CAR T-cell products in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express mesothelin (MSLN) and have lost HLA-A\*02 expression.
The main questions this study aims to answer are:
Phase 1: What is the recommended dose that is safe for patients
Phase 2: Does the recommended dose kill 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
Tmod CAR T cells at the assigned dose
The main questions this study aims to answer are:
Phase 1: What is the recommended dose that is safe for patients
Phase 2: Does the recommended dose kill 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
Tmod CAR T cells at the assigned dose
Detailed Description:
This is a seamless phase 1/2, multi-center, open-label study that enrolls adults with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, OVCA, MESO or other solid tumors with MSLN expression. Subjects must be germline HLA-A\*02 heterozygous, with tumors that express MSLN and have lost HLA-A\*02 expression. This study has two arms: Arm 1 is a study of A2B694 and Arm 2 is a study of A2B543.
The purpose of Phase 1 of this study is to determine the safety and the optimal dose of the Tmod products (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 the Tmod products.
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 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have loss of heterozygosity \[LOH\] for HLA-A\*02 protein). Additionally, normal healthy cells that maintain HLA-A\*02 expression and co-express MSLN (eg, lung 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-2) and the participant's T cells are manufactured and then infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course.
The purpose of Phase 1 of this study is to determine the safety and the optimal dose of the Tmod products (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 the Tmod products.
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 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have loss of heterozygosity \[LOH\] for HLA-A\*02 protein). Additionally, normal healthy cells that maintain HLA-A\*02 expression and co-express MSLN (eg, lung 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-2) and the participant's T cells are manufactured and then infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: