A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (EVEREST-1)
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| ClinicalTrials.gov Identifier: NCT05736731 |
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Recruitment Status :
Recruiting
First Posted : February 21, 2023
Last Update Posted : April 9, 2024
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Biological: A2B530 Diagnostic Test: xT-Onco with HLA-LOH Assay | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 160 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B530, an Autologous Logic-gated Tmod™ Chimeric Antigen Receptor T Cell (CAR T), in Heterozygous HLA-A*02 Adult Subjects With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression |
| Actual Study Start Date : | April 28, 2023 |
| Estimated Primary Completion Date : | December 2026 |
| Estimated Study Completion Date : | December 2028 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: A2530
Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B530 intravenously on day 0
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Biological: A2B530
Autologous logic-gated Tmod CAR T-cells
Other Name: Tmod CAR T-cell Therapy Diagnostic Test: xT-Onco 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 A2B530 infusion. ]Adverse Events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 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 A2B530 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 A2B530 infusion ]The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.
- Persistence of A2B530 [ Time Frame: up to 24 months post A2B530 infusion ]Number of A2B530 Tmod CAR T cells present in patients treated with A2B530 as assessed by Polymerase Chain Reaction (PCR) (or similar method) on participant blood samples
- Cytokine analysis [ Time Frame: up to 24 months post A2B530 infusion ]Cytokine levels in patients treated with A2B530 assessed by cytokine analysis on participant blood samples
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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): NCT05736731
| Contact: Clinical Trials | 310-431-9180 | ClinicalTrials@a2bio.com |
| United States, Arizona | |
| Banner Health | Recruiting |
| Gilbert, Arizona, United States, 85234 | |
| Contact: Matthew Ulrickson, MD | |
| Contact: Yasmin Adam yasmin.adam2@bannerhealth.com | |
| United States, California | |
| City of Hope | Recruiting |
| Duarte, California, United States, 90101 | |
| Contact: Janela Agonoy jagonoy@coh.org | |
| Principal Investigator: Marwan Fakih, MD | |
| University of California San Diego | Recruiting |
| La Jolla, California, United States, 92093 | |
| Contact: Sandip Patel, MD | |
| Contact: Jona Plevin 8582463253 jplevin@health.ucsd.edu | |
| UCLA Medical Center | Recruiting |
| Los Angeles, California, United States, 90404 | |
| Contact: Christopher Hannigan channigan@mednet.ucla.edu | |
| Principal Investigator: J. Randolph Hecht, MD | |
| Stanford University | Recruiting |
| Stanford, California, United States, 94305 | |
| Contact: Shruti Murthy shrutide@stanford.edu | |
| Principal Investigator: Wen-Kai Weng, MD, PhD | |
| United States, Florida | |
| Moffitt Cancer Center | Recruiting |
| Tampa, Florida, United States, 33136 | |
| Contact: Rebecca Delph Rebecca.Delph@moffitt.org | |
| Principal Investigator: Kedar Kirtane | |
| United States, Minnesota | |
| Mayo Clinic Rochester | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Mohammed Elhaj elhaj.mohammed@mayo.edu | |
| Principal Investigator: Julian Molina, MD, PhD | |
| United States, Missouri | |
| Washington University | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| Contact: Amberly Scott amberly@wustl.edu | |
| Principal Investigator: Patrick Grierson, MD PhD | |
| United States, New York | |
| NYU Langone Medical Center | Recruiting |
| New York, New York, United States, 10016 | |
| Contact: Salman Punekar, MD 212-731-6228 Salman.Punekar@nyulangone.org | |
| Contact: Maria Herrmann maria.herrmann@nyulangone.org | |
| Principal Investigator: Salman Punekar, MD | |
| United States, Texas | |
| MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: GI Clinical Trials GIClinicalTrials@mdanderson.org | |
| Principal Investigator: Maria Pia Morelli, MD, PhD | |
| Study Director: | Eric Ng, MD | Sr. Medical Director, Safety, A2 Biotherapeutics, Inc. |
Publications:
| Responsible Party: | A2 Biotherapeutics Inc. |
| ClinicalTrials.gov Identifier: | NCT05736731 |
| Other Study ID Numbers: |
A2B530-101 |
| First Posted: | February 21, 2023 Key Record Dates |
| Last Update Posted: | April 9, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Study data will be shared within 1 year of study completion. |
| Supporting Materials: |
Clinical Study Report (CSR) |
| Time Frame: | Data will be available within 1 year of the completion of the study, the length of time of availability is to be determined. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | Yes |
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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 |
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Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Pancreatic Neoplasms Recurrence Disease Attributes Pathologic Processes Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Endocrine Gland Neoplasms Pancreatic Diseases Endocrine System Diseases |