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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

ConditionsSolid Tumor, AdultColorectal CancerNSCLCNon Small Cell Lung CancerNSCLC, RecurrentNon-Small Cell Squamous Lung CancerPancreas CancerPancreatic NeoplasmColorectal AdenocarcinomaCRCColon CancerRectal CancerCancerOvarian CancerOvarian NeoplasmsMesotheliomaMesothelioma, MalignantOvary CancerLung CancerMESOM
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorA2 Biotherapeutics Inc.

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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.

Received previous required therapy for the appropriate solid tumor disease as described in the protocol

Has adequate organ function as described in the protocol

Disqualifiers

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

MESO with pleural involvement extending into the peritoneum

Trial design

Design model

Parallel

Treatments tested in this trial

  • A2B694

    Biological/Vaccine

    Autologous logic-gated Tmod CAR T cells

  • A2B543

    Biological/Vaccine

    Autologous logic-gated Tmod CAR T cells

  • xT CDx with HLA-LOH Assay

    Diagnostic test

    An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device

Treatment groups

474 Participants
are divided into 2 treatment groups
Group A: Arm 1: A2B694Experimental treatment 2 interventions
Group B: Arm 2: A2B543Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level

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.

Time frame
From the time of Informed consent until 24 months (2 years) post infusion
2

Phase 1: Recommended Phase 2 Dose (RP2D)

The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.

Time frame
21 days post infusion
3

Phase 2: The Overall Response Rate (ORR) for patients

The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.

Time frame
24 months post infusion

Secondary outcomes

1

Persistence of Tmod product

Number of Tmod CAR T cells present as assessed by polymerase chain reaction (PCR) (or similar method) on participant blood samples

Time frame
up to 24 months post infusion
2

Cytokine analysis

Cytokine levels such as interferon-gamma (IFN-γ) and interleukin-6 (IL-6) assessed by cytokine analysis on participant blood samples

Time frame
up to 24 months post infusion

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

A2 Biotherapeutics Inc.

Lead sponsor

Tempus AI

Collaborator

Source ClinicalTrials.gov
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