CAR T Cells in Mesothelin-Expressing Breast Cancer

Launched by UNIVERSITY OF PENNSYLVANIA · Nov 11, 2022

Keywords

ClinConnect Summary

This clinical trial, titled "CAR T Cells in Mesothelin-Expressing Breast Cancer," is exploring a new treatment approach for patients with advanced breast cancer that is difficult to treat. Specifically, it focuses on patients with triple-negative breast cancer, which means their tumors do not express certain hormone receptors or the HER2 protein. The main goal of this Phase 1 trial is to test the safety of CAR T cell therapy, a type of treatment that uses the body’s own immune cells to fight cancer, while also checking if it works effectively.

To be eligible for this trial, participants must be at least 18 years old and have a specific type of breast cancer that cannot be surgically removed or has spread to other parts of the body. They must also have a tumor that shows a certain level of a protein called mesothelin. Patients will need to have a lesion (a specific area of abnormal tissue) that can be accessed for treatment and must be in good overall health, meaning their organs and blood counts are functioning well. Participants will receive the CAR T cell therapy, and closely monitored for any side effects or responses to the treatment. It’s important to note that the trial is currently recruiting participants, so those who meet the criteria and are interested can consider joining.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• 1. Patients with locally advanced unresectable or metastatic triple-negative breast cancer as confirmed by all of the following:
• • 1. ER-negative or low-ER positive (≤ 10% by IHC)
• • 2. PR-negative or low-PR positive (≤ 10% by IHC)
• • 3. HER2 negative by IHC/FISH
• • 2. Patients with an accessible lesion that can be targeted for both intratumoral injection and surgical excision/biopsy by either a surgeon or interventional radiology.
• • 3. Confirmed tumor mesothelin expression by ≥ 10% of malignant cells by IHC.
• • 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 5. Adequate organ and bone marrow function defined as:
• • 1. Bilirubin ≤ 2.0 x ULN
• • 2. Serum Creatinine ≤ 1.5 x ULN
• • 3. ALT/AST ≤ 3 x ULN
• • 4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• • 5. Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram
• • 6. Male and female patients ≥ 18 years of age.
• • 7. Provides written informed consent.
• • 8. Subjects of reproductive potential must agree to use acceptable birth control methods
• Exclusion Criteria:
• • 1. Active invasive cancer other than the study-targeted malignancy.
• 2. Evidence of active hepatitis B or hepatitis C. The following would not qualify as an active infection, thus would not exclude the subject from participating:
• • 1. Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
• • 2. Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
• • 3. Patients with ongoing or active infection.
• • 4. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg/day of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• • 5. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (≤ 10mg daily equivalent of prednisone). Use of inhaled or topical steroids is allowable.
• • 6. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• • 7. Pregnant or breastfeeding women.
• • 8. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected.
• 9. Patients with significant lung disease as follows:
• • 1. Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.
• • 2. Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
• • 3. Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc).
• • 10. Patients with active central nervous system (CNS) involvement. Screening for this (e.g. lumbar puncture, brain MRI, etc) is not required unless the patient is symptomatic and/or radiographic findings are present.