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
Purpose
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
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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- 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 Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental A2B694 |
Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B694 intravenously on day 0 |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- A2 Biotherapeutics Inc.
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.