CART-GFRa4 Cells after Lymphodepletion for the Treatment of Medullary Thyroid Cancer

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
• Serum creatinine =< 2.5 mg/dl or estimated creatinine clearance >= 30 ml/min and not on dialysis
• Aspartate aminotransferase (AST) =< 5 x 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 echocardiography (ECHO)/multigated acquisition scan (MUGA)
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea and pulse oxygen > 92% on room air
• Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1
• Toxicities from prior therapies must have recovered to grade =< 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria or to the patient’s prior baseline
• Patients must have evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Subjects of reproductive potential must agree to use acceptable birth control methods
• Female patients of reproductive potential (women who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone a sterilization procedure [hysterectomy or bilateral oophorectomy]) must have negative pregnancy test performed at the time of enrollment and a negative serum pregnancy test prior to study treatment. Due to the unknown risks of the CART-GFRa4 cells with respect to pregnancy, as well as risks associated with lymphodepleting chemotherapy, it is recommended that all subjects of reproductive potential use at least one medically acceptable form of contraception for at least 1 year after their infusion of CART-GFRa4 cells. Investigators shall counsel subjects on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Medically acceptable forms of birth control include one of the following methods: * Total abstinence * Condoms (male or female) with or without a spermicidal agent * Diaphragm or cervical cap with spermicide * Hormonal/non-hormonal intrauterine device (IUD) * Hormonal-based contraception Patients who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingectomy, and/or bilateral oophorectomy or men who have documented azoospermia) do not require the use of contraception. Acceptable documentation of sterilization, azoospermia, or menopause consists of written or oral attestation by a physician or a physician’s staff in one of the following formats: * Physician report/letter * Operative report or other source documentation in the subject’s medical record (a laboratory report of azoospermia is required to document successful vasectomy) * Discharge summary * Laboratory report of azoospermia * Follicle stimulating hormone measurement elevated into the menopausal range

Exclusion Criteria

• Active hepatitis B or hepatitis C infection
• 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 (estimated glomerular filtration rate [eGFR] or creatinine clearance [CrCl] 59-30 ml/min/1.73 m^2)
• 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
• 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 multiple sclerosis [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 magnetic resonance imaging [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 cerebrospinal fluid (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, dimethyl sulfoxide [DMSO], and dextran 40).