MOv19-BBz CAR T cell treatment for FRa-positive lung cancer

Phase I Clinical Trial of Autologous Folate Receptor-Alpha Redirected T Cells in Patients With FRa+ Cancers

This trial will test whether a single intrapleural infusion of MOv19-BBz CAR T cells given after lymphodepleting chemotherapy is safe and can help control FRa-positive metastatic or recurrent non-small cell lung cancer with malignant pleural effusion.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, CAR T
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT07116057 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label trial of intrapleural MOv19-BBz CAR T cells administered as a single dose following lymphodepleting chemotherapy to patients with FRa-positive metastatic or recurrent non-small cell lung cancer and malignant pleural effusion. Tumor FRa expression must be documented by IHC (≥10% of tumor cells) on archived tissue tested at the University of Pennsylvania. Patients without an existing pleural catheter will have a temporary catheter placed to allow intrapleural infusion, and treatment with commercial checkpoint inhibitors may be resumed at least 28 days after CAR T infusion per routine care. The primary focus is safety and feasibility with collection of preliminary signals of antitumor activity.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic or recurrent FRa-positive non-small cell lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion who have failed at least one prior standard systemic therapy and meet organ function and other eligibility requirements.

Not a fit: Patients whose tumors lack FRa expression, who do not have malignant pleural effusion, who have uncontrolled CNS disease or poor organ function, or who cannot undergo intrapleural catheter placement are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this targeted intrapleural CAR T approach could better control pleural disease and potentially extend disease control for patients with FRa-positive NSCLC.

How similar studies have performed: CAR T therapies have shown major success in blood cancers but limited and early results in solid tumors, and intrapleural CAR T and FRa-targeting approaches remain novel with only preliminary early-phase data.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent form
2. 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.
3. 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.
4. Patients must have evidence of active disease as defined by RECIST 1.1 criteria
5. 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

   1. No concurrent treatment for the CNS disease
   2. No progression of CNS metastasis on MRI at screening
   3. No evidence of leptomeningeal disease or cord compression
6. Adequate organ function defined as:

   1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; Patient must not be on dialysis
   2. ALT/AST ≤ 3x upper limit of normal range
   3. 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)
   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) ≥ 40% confirmed by ECHO or MUGA
7. Male or female age ≥ 18 years
8. Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
9. Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.

Exclusion Criteria:

1. Any clinically significant pleural effusion that cannot be drained with standard approaches.
2. 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.Note: "Greater than lobar" = "in more than 1 lobe".
   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.).
   4. Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
3. Active hepatitis B or hepatitis C infection
4. Any other active, uncontrolled infection
5. Class III/IV cardiovascular disability according to the New York Heart Association Classification
6. Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
7. Dependence on systemic steroids or immunosuppressant medications.
8. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Andrew Haas, MD, PhD — University of Pennsylvania
• Study coordinator: Abramson Cancer Center Clinical Trials Service

Conditions Metastatic Non Small Cell Lung Cancer; Recurrent Lung Non-Small Cell Carcinoma; NSCLC; CAR T cells; FRa+; lung cancer; lung adenocarcinoma