Study of AIC100 in Relapsed/Refractory Thyroid Cancer
A Multi Center Phase I Study of AIC100 in Relapsed and/or Refractory Advanced Thyroid Cancer and Anaplastic Thyroid Cancer
Lead SponsorCornell University
Indication/ConditionAnaplastic Thyroid Cancer Relapsed/Refractory Poorly Differentiated Thyroid Cancer
Intervention/TreatmentAIC100 CAR T Cells
The purpose of this study is to assess the safety and tolerability and determine the recommended dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer.
The primary objective of this study is to assess the safety and tolerability and determine the recommended dose of AIC100 for phase 2 study in patients with relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic thyroid cancer that are BRAF wild-type, or BRAF mutant anaplastic thyroid cancer after failure of BRAF-mutant specific therapy.
Upon enrollment, patients will undergo apheresis for collection of autologous lymphocytes. The autologous T cells will be transfected and expanded in-vitro to generate the AIC100 product. After lymphodepleting therapy, AIC100 will be infused.
The study drug, AIC100, consists of autologous CAR T cells targeting intercellular adhesion molecule-1 (ICAM-1) on thyroid cancer. In addition, AIC100 cells express the somatostatin receptor subtype 2 (SSTR2), which should enable CAR T cell imaging in the patient.
Autologous CAR T cells directed against ICAM-1
AIC100 Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells
AIC100 Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells
AIC100 Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells
AIC100 Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR Tcells
Inclusion Criteria: Willing and able to participate in the study and provide written informed consent. One of the following thyroid malignancies: Anaplastic Thyroid Cancer (ATC), BRAF wild-type at any stage including newly diagnosed. Anaplastic Thyroid Cancer (ATC) BRAF mutant after failure of BRAF specific therapy. Poorly differentiated thyroid cancer that has failed surgery, radioactive iodine, chemotherapy, radiation therapy and/or targeted therapies. Measurable disease (by Computed Tomography [CT] scan or Positron Emission Tomography/Computed Tomography [PET/CT]) Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Life expectancy of greater than 8 weeks. Adequate hepatic, renal, bone marrow, and coagulation function defined as: Estimated creatinine clearance >= 50 ml/min Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x the upper limit of normal (ULN); subjects with hepatic metastases ALT and AST <= 5.0 x ULN Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin <= 3 mg/dL Serum albumin >= 2.5 g/dL Has recovered by toxicity or prior anticancer therapy to Grade 0-1 Absolute lymphocyte count (ALC) >= 100/mm3 prior to apheresis Females of reproductive potential must agree to use one highly effective method of contraception and one additional effective method from at least 28 days prior to beginning study therapy, during study therapy including dose interruptions, and for 1 year after the last dose of study therapy. Females of reproductive potential must have a negative serum beta human chorionic gonadotropin pregnancy test result at screening and within 7 days prior to the first dose of study therapy. Detectable ICAM-1 expression on tumor by immunohistochemistry Exclusion Criteria: Women who are pregnant or breastfeeding. Active systemic infections that are not controlled. Previous treatment with investigational gene therapy or chimeric antigen receptor therapy. Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke as well as symptomatic or uncontrolled brain metastases. Evidence of another malignancy within 2 years prior to Screening (except in situ non- melanoma skin cell cancers and localized controlled prostate cancer) Patients with seropositive response of human immunodeficiency virus (HIV) or uncontrolled hepatitis B virus or hepatitis C virus infections. Active autoimmune disease (including but not limited to: systemic lupus erythematous, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation by Investigator, with the exception of thyroid replacement. Patients with severe chronic diseases of kidney, liver, heart, lung or any other serious illnesses that the Investigator consider may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, auto-immune disorders, metabolic diseases, infectious diseases. Patients who need long-term use of systemic steroids. Allergy to any of the chemotherapy drugs given during lymphodepletion.