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)

April 7, 2024 updated by: A2 Biotherapeutics Inc.

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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. 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

Enrollment (Estimated)

230

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UCSD Moores Cancer Center
        • Principal Investigator:
          • Sandip Patel, MD
        • Contact:
      • Los Angeles, California, United States, 90404
        • Recruiting
        • UCLA Medical Center
        • Principal Investigator:
          • J. Randolph Hecht, MD
        • Contact:
      • Stanford, California, United States, 94305
        • Not yet recruiting
        • Stanford University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • Yanyan Lou, MD
        • Contact:
      • Tampa, Florida, United States, 33606
        • Not yet recruiting
        • Moffitt Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Not yet recruiting
        • Massachusetts General Hopsital/Dana Farber Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Principal Investigator:
          • Julian Molina, MD, PhD
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Contact:
          • Amberly Scott
        • Contact:
    • New York

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Key Inclusion Criteria:

  1. Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A*02 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, OVCA, MESO, or other solid tumors with MSLN expression. Measurable disease is required with lesions of >1.0 cm by CT.
  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. MESO with pleural involvement extending into the peritoneum
  5. Cancer therapy within 3 weeks or 3 half lives of A2B694 infusion
  6. Radiotherapy within 28 days of A2B694 infusion
  7. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months
  8. 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
  9. History of interstitial lung disease including drug-induced interstitial lung disease and radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year
  10. Requires supplemental home oxygen
  11. Females of childbearing potential who are pregnant or breastfeeding
  12. 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 A2B694

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A2B694
Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B694 intravenously on day 0
Biological: A2B694
Autologous logic-gated Tmod CAR T cells
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From the time of Informed consent until 24 months (2 years) post A2B694 infusion
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.
21 days post A2B694 infusion
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.
24 months post A2B694 infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 24 months post A2B694 infusion
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
up to 24 months post A2B694 infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

A2 Biotherapeutics Inc.

Collaborators

Tempus AI

Investigators

  • Study Director: John Welch, MD, PhD, A2 Biotherapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2024

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2029

Study Registration Dates

First Submitted

September 18, 2023

First Submitted That Met QC Criteria

September 21, 2023

First Posted (Actual)

September 25, 2023

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 7, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A2B694-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study data will be shared within 1 year of study completion.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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