CAR T Cells in Mesothelin-Expressing Breast Cancer

• Status: Not yet recruiting
• Trial end date: 2038-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Phase 1 - Safety and Proof of Concept

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania

Criteria

Inclusion Criteria:

1. Patients with locally advanced unresectable or metastatic breast cancer with one of the following diagnoses:

a. Triple negative disease as confirmed by all of the following: i. ER-negative or low-ER positive (≤ 10% by IHC) ii. PR-negative or low-PR positive (≤ 10% by IHC) ii. HER2 negative by IHC/FISH b. HER2 positive 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 active radiation pneumonitis