Recruiting
Phase 1/2
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
Condition(s) studied
Solid Tumor, AdultColorectal CancerNSCLCNon Small Cell Lung CancerNSCLC, RecurrentNon-Small Cell Squamous Lung CancerPancreas CancerPancreatic NeoplasmColorectal AdenocarcinomaCRCColon CancerRectal CancerCancerOvarian CancerOvarian NeoplasmsMesotheliomaMesothelioma, MalignantOvary CancerLung CancerMESOM
Investigational drug(s) / intervention(s)
A2B694A2B543xT CDx with HLA-LOH Assay
A2B694: Autologous logic-gated Tmod CAR T cells
A2B543: Autologous logic-gated Tmod CAR T cells
xT CDx with HLA-LOH Assay: An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device
Study 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
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
Primary outcome measure(s)
- Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level — From the time of Informed consent until 24 months (2 years) post 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.
- Phase 1: Recommended Phase 2 Dose (RP2D) — 21 days post 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 — 24 months post infusion
The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.
Trial sites (12)
| Facility | City | Region | Status |
| Banner Health |
Gilbert |
Arizona |
Recruiting |
| UCSD Moores Cancer Center |
La Jolla |
California |
Recruiting |
| UCLA Medical Center |
Los Angeles |
California |
Recruiting |
| Stanford University |
Stanford |
California |
Recruiting |
| Mayo Clinic |
Jacksonville |
Florida |
Recruiting |
| Moffitt Cancer Center |
Tampa |
Florida |
Recruiting |
| Mayo Clinic Rochester |
Rochester |
Minnesota |
Recruiting |
| Washington University |
St Louis |
Missouri |
Recruiting |
| NYU Langone Medical Center |
New York |
New York |
Recruiting |
| The Ohio State University Comprehensive Cancer Center |
Columbus |
Ohio |
Recruiting |
| Vanderbilt University Medical Center |
Nashville |
Tennessee |
Recruiting |
| Fred Hutchinson Cancer Center |
Seattle |
Washington |
Recruiting |