A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Subjects With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression (EVEREST-2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT06051695|
Recruitment Status : Not yet recruiting
First Posted : September 25, 2023
Last Update Posted : November 13, 2023
The goal of this study is to test A2B694, 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), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express MSLN and have lost HLA-A*02 expression.
The main questions this study aims to answer are:
Phase 1: What is the recommended dose of A2B694 that is safe for patients
Phase 2: Does the recommended dose of A2B694 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
A2B694 Tmod CAR T cells at the assigned dose
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor, Adult Colorectal Cancer NSCLC Non Small Cell Lung Cancer NSCLC, Recurrent Non-Small Cell Squamous Lung Cancer Pancreas Cancer Pancreatic Neoplasm Colorectal Adenocarcinoma CRC Colon Cancer Rectal Cancer Cancer Ovarian Cancer Ovarian Neoplasms Mesothelioma Mesothelioma, Malignant Ovary Cancer Lung Cancer MESOM||Biological: A2B694 Diagnostic Test: xT CDx with HLA-LOH Assay||Phase 1 Phase 2|
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. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B694 (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 A2B694.
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 A2B694 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||230 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B694, an Autologous Logic-gated Tmod™ CAR T, 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|
|Estimated Study Start Date :||March 2024|
|Estimated Primary Completion Date :||June 2028|
|Estimated Study Completion Date :||June 2029|
Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B694 intravenously on day 0
Autologous logic-gated Tmod CAR T cells
Other Name: Tmod CAR T-cell Therapy
Diagnostic Test: xT CDx with HLA-LOH Assay
An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device
- Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level [ Time Frame: From the time of Informed consent until 24 months (2 years) post A2B694 infusion ]Adverse Events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version (CTCAE) 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.
- Phase 1: Recommended Phase 2 Dose (RP2D) [ Time Frame: 21 days post A2B694 infusion ]The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.
- Phase 2: The Overall Response Rate (ORR) for patients [ Time Frame: 24 months post A2B694 infusion ]The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.
- Persistence of A2B694 [ Time Frame: up to 24 months post A2B694 infusion ]Number of A2B694 Tmod CAR T cells present in patients treated with A2B694 as assessed by Polymerase Chain Reaction (PCR) (or similar method) on participant blood samples
- Cytokine analysis [ Time Frame: up to 24 months post A2B694 infusion ]Cytokine levels such as interferon-gamma (IFN-γ) and interleukin-6 (IL-6) in patients treated with A2B694 assessed by cytokine analysis on participant blood samples
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06051695
|Contact: Clinical Trials||310-431-9180||ClinicalTrials@a2bio.com|
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|UCSD Moores Cancer Center|
|La Jolla, California, United States, 92093|
|UCLA Medical Center|
|Los Angeles, California, United States, 90404|
|Stanford, California, United States, 94305|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33606|
|United States, Massachusetts|
|Massachusetts General Hopsital/Dana Farber Cancer Center|
|Boston, Massachusetts, United States, 02114|
|United States, Minnesota|
|Mayo Clinic Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|NYU Langone Medical Center|
|New York, New York, United States, 10016|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Director:||John Welch, MD, PhD||A2 Biotherapeutics|