MOv19-BBz CAR T Cells in FRa+ Cancers
Phase I Clinical Trial of Autologous Folate Receptor-Alpha Redirected T Cells in Patients With FRa+ Cancers
University of Pennsylvania
10 participants
Oct 7, 2025
INTERVENTIONAL
Conditions
Summary
This is a Phase I open-label clinical trial to assess the safety, feasibility, and preliminary efficacy of intrapleural administration of MOv19-BBz CAR T cells in patients with FRa+ cancers. This study will be initiated in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) only. Subjects will receive a single dose of MOv19-BBz CAR T cells via intrapleural infusion following lymphodepleting chemotherapy. Subjects without an existing intra-pleural catheter will have a temporary pleural catheter placed for the study. Subjects may initiate treatment with commercial checkpoint inhibitors per routine care beginning at least 28 days after receiving MOv19-BBz CAR T cells.
Eligibility
Inclusion Criteria19
- Signed informed consent form
- Documentation of tumor FRa expression by IHC at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available.
- Disease-specific criteria:
- a. NSCLC Patients: i. Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion.
- ii. Failure of at least one prior line of standard of care therapy for advanced stage disease.
- Patients must have evidence of active disease as defined by RECIST 1.1 criteria
- Patients with asymptomatic CNS metastases that have been treated (and are off steroids for the treatment of CNS disease) are allowed. They must meet the following criteria
- No concurrent treatment for the CNS disease
- No progression of CNS metastasis on MRI at screening
- No evidence of leptomeningeal disease or cord compression
- Adequate organ function defined as:
- Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; Patient must not be on dialysis
- ALT/AST ≤ 3x upper limit of normal range
- Serum total bilirubin ≤ 1.5 mg/dl, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤ 3.0 mg/dl)
- 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) ≥ 40% confirmed by ECHO or MUGA
- Male or female age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
- Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.
Exclusion Criteria14
- Any clinically significant pleural effusion that cannot be drained with standard approaches.
- 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.Note: "Greater than lobar" = "in more than 1 lobe".
- 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 radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
- Active hepatitis B or hepatitis C infection
- Any other active, uncontrolled infection
- Class III/IV cardiovascular disability according to the New York Heart Association Classification
- Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
- Dependence on systemic steroids or immunosuppressant medications.
- Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
- Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
Interventions
Autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with FRa specificity.
Cytotoxic chemotherapy agents used for lymphodepletion prior to MOv19-BBz CAR T cell administration.
Laboratory Developed Test used to determine subject eligibility
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07116057