CAR T Cells in Mesothelin-Expressing Breast Cancer

NCT05623488 | Terminated Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: UPCC# 15122, IRB # 852205
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 - Safety and Proof of Concept

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Occurrence of treatment-limiting toxicities (TLTs)

  90 days

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0.

  15 years

Secondary Outcomes (7)

• Proportion of manufacturing product that do not meet the release criteria.

  60 days

• Proportion of the products that meet the target dose.

  60 days

• Proportion of enrolled subjects that receive study treatment.

  60 days

• Proportion of eligible subjects that receive study treatment

  60 days

• Proportion of subjects for which standard of care treatment is not impacted due to CAR T cell related toxicity.

  90 days

Study Arms (2)

Dose Level 1

EXPERIMENTAL

3.00 x 10\^7 CAR T cells administered intratumoral

Drug: huCART-meso cells; Device: Mesothelin Expression Testing

Dose Level -1

EXPERIMENTAL

3.00 x 10\^6 CAR T cells administered intratumoral

Drug: huCART-meso cells; Device: Mesothelin Expression Testing

Interventions

huCART-meso cells DRUG

Autologous T cells lentivirally transduced with chimeric anti-mesothelin immunoreceptor M5 scFv fused to the 4-1BB and CD3ζ signaling domains

Dose Level -1; Dose Level 1

Mesothelin Expression Testing DEVICE

Laboratory Developed Test

Dose Level -1; Dose Level 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with locally advanced unresectable or metastatic triple-negative breast cancer as confirmed by all of the following:
• ER-negative or low-ER positive (≤ 10% by IHC)
• PR-negative or low-PR positive (≤ 10% by IHC)
• HER2 negative by IHC/FISH
• Patients with an accessible lesion that can be targeted for both intratumoral injection and surgical excision/biopsy by either a surgeon or interventional radiology.
• Confirmed tumor mesothelin expression by ≥ 10% of malignant cells by IHC.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and bone marrow function defined as:
• Bilirubin ≤ 2.0 x ULN
• Serum Creatinine ≤ 1.5 x ULN
• ALT/AST ≤ 3 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram
• Male and female patients ≥ 18 years of age.
• Provides written informed consent.

You may not qualify if:

• Active invasive cancer other than the study-targeted malignancy.
• 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:
• Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
• Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
• Patients with ongoing or active infection.
• 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.
• 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.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Pregnant or breastfeeding women.
• 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.
• Patients with significant lung disease as follows:
• 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.
• Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
• 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).
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Julia Tchou, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: November 21, 2022
• Study Start: February 6, 2023
• Primary Completion: April 7, 2025
• Study Completion: April 7, 2025
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)