MOv19-BBz CAR T Cells in FRa+ Cancers

NCT07116057 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 858800 (UPCC #06525)R01CA260902
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Non Small Cell Lung Cancer; Recurrent Lung Non-Small Cell Carcinoma

Keywords

NSCLC; CAR T cells; FRa+; lung cancer; lung adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events as assessed by CTCAE V5.0

  Type, frequency, severity, and attribution of adverse events.

  Up to 15 years post-MOv19-BBz CAR T cell administration

• Occurrence of treatment-limiting toxicities (TLTs)

  Unacceptable toxicity as defined by the protocol.

  28 days post-MOv19-BBz CAR T cell administration

Secondary Outcomes (5)

• Evaluate study feasibility

  6 months

• Objective Response Rate (ORR)

  Up to 12 months following treatment with MOv19-BBz CAR T cells

• Duration of Response (DOR)

  Up to 15 years following treatment with MOv19-BBz CAR T cells

• Progression Free Survival (PFS)

  Up to 15 years following treatment with MOv19-BBz CAR T cells

• Overall Survival (OS)

  Up to 15 years following treatment with MOv19-BBz CAR T cell

Study Arms (2)

Dose Level 1 (DL1)

EXPERIMENTAL

single dose of 5x10(7) MOv19-BBz CAR T cells administered via intrapleural infusion following lymphodepleting chemotherapy

Biological: MOv19-BBz CAR T cells; Drug: Cyclophosphamide/Fludarabine; Device: FRa Expression Testing

Dose Level -1 (DL-1)

EXPERIMENTAL

2.5x10(7) MOv19-BBz CAR T cells adminstered via intrapleural infusion, following lymphodepleting chemotherapy. This dose level will only be explored if ≥ 2 TLTs occur at any time in DL1.

Biological: MOv19-BBz CAR T cells; Drug: Cyclophosphamide/Fludarabine; Device: FRa Expression Testing

Interventions

MOv19-BBz CAR T cells BIOLOGICAL

Autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with FRa specificity.

Dose Level -1 (DL-1); Dose Level 1 (DL1)

Cyclophosphamide/Fludarabine DRUG

Cytotoxic chemotherapy agents used for lymphodepletion prior to MOv19-BBz CAR T cell administration.

Dose Level -1 (DL-1); Dose Level 1 (DL1)

FRa Expression Testing DEVICE

Laboratory Developed Test used to determine subject eligibility

Dose Level -1 (DL-1); Dose Level 1 (DL1)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

CF regimen

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Andrew Haas, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

Study Design

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

Model Details: Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1.

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: August 11, 2025
• Study Start: October 7, 2025
• Primary Completion (Estimated): October 1, 2040
• Study Completion (Estimated): October 1, 2040
• Last Updated: October 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)