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
This study tests a new type of immunotherapy called logic-gated CAR T cells that are designed to target cancer cells expressing mesothelin, a protein found on several solid tumors. The CAR T cells are created from your own immune cells and modified to recognize and attack cancer cells while avoiding healthy tissue. The research aims to evaluate how safe and effective this treatment is for patients with colorectal, pancreatic, lung, ovarian, or other solid tumors.
Key Objective: This trial is testing whether logic-gated CAR T cells can safely and effectively treat solid tumors that express mesothelin by harnessing the patient's own immune system to target and destroy cancer cells.
Who to Consider: Adults with mesothelin-expressing solid tumors (such as colorectal, pancreatic, lung, or ovarian cancer) who have lost HLA-A*02 expression and have exhausted standard treatment options should consider enrolling.
Trial Parameters
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
Eligibility Criteria
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