MOv19-BBz CAR T Cells for the Treatment of Folate Receptor Alpha Positive Metastatic and Recurrent Non-small Cell Lung Cancer

Inclusion Criteria

• Signed informed consent form
• Documentation of tumor FRalpha expression by immunohistochemistry (IHC) at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available
• Disease-specific criteria: * NSCLC patients: ** Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion ** Failure of at least one prior line of standard of care therapy for advanced stage disease
• Patients must have evidence of active disease
• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; patient must not be on dialysis
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 x 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 Criteria

• Any clinically significant pleural effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to eligibility confirmation by physician-investigator is acceptable
• 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
• Patients with symptomatic CNS metastases. Patients with asymptomatic CNS metastases that have been treated and are no longer on anti-inflammatory/edema steroids are allowed
• 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. For additional details regarding use of steroid and 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 multiple sclerosis [MS]) will be excluded
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and dextran 40)