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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• Email: PMCancerResearch@pennmedicine.upenn.edu
• Phone: 215-349-8245

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.