GFRα4 CAR T Cells in MTC Patients

Inclusion criteria

• Signed, written informed consent
• Male or female age ≥ 18 years
• Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC).
• Incurable recurrent/metastatic disease that is progressive after at least 1 prior tyrosine kinase inhibitor (TKI) containing regimen, or the patient was intolerant of or declined such therapy.
• Adequate organ function defined as:

• Serum creatinine ≤ 2.5 mg/dl or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
• AST ≤ 5x upper limit of normal range and total bilirubin ≤ 2.0 mg/dl; except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome.
• Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen greater than 92% on room air.
• ECOG Performance Status that is either 0 or 1.
• Toxicities from prior therapies must have recovered to grade ≤ 2 according to the CTCAE 5.0 criteria or to the patient's prior baseline.
• Patients must have evaluable disease as defined by RECIST 1.1.
• Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion criteria

• Evidence of active hepatitis B or hepatitis C infection. The following would not qualify as an active infection, thus would not exclude the subject from participating

• Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
• Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
• Any other active, uncontrolled infection.
• Any prior history of moderate to severe (Grade 2 or higher) pneumonitis.
• Subjects with chronic kidney disease with Grade 2 or higher renal impairment (eGFR or CrCl 59-30 ml/min/1.73 m2).
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (≤10mg equivalent of prednisone). Use of inhaled steroids is allowable. Corticosteroid treatment as anti-emetic prophylaxis on the day of lymphodepleting chemotherapy administration is allowed per institutional practice.
• Any moderate to severe skin rash or allergies requiring systemic treatment.
• Receipt of immune checkpoint inhibitors within 2 months prior to physician-investigator confirmation of eligibility - Retired with Protocol Version 3.
• Pregnant or nursing (lactating) women.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson's) will be excluded.
• Have any history of prior or active central nervous system (CNS) involvement (e.g., leptomeningeal disease, parenchymal masses) with MTC. Screening for this (e.g., with lumbar puncture and/or brain MRI) is not required unless suspicious symptoms and/or radiographic findings are present. Subjects with calvarial metastatic disease that extends intracranially and involves the dura will be excluded, even if CSF is negative for MTC.
• Known seizure disorder or history of prior seizures requiring medication.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).