A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, 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

Trial ID: NCT06051695

Interventional - Phase 1/2 - Recruiting

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

Conditions

• 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

Interventions

• A2B694
• A2B543
• xT CDx with HLA-LOH Assay

Eligibility

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 infusion
• 6. Radiotherapy within 28 days of 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

Sponsor

A2 Biotherapeutics Inc., Tempus AI

Source: ClinicalTrials.gov

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