The purpose of this study is to assess the safety 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 determine the recommended
dose of AIC100 for phase II 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 leukapheresis 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 containing the I domain of
lymphocyte function-associated antigen-1 (LFA-1) and targeting its over-expressed
physiological ligand, intercellular adhesion molecule-1 (ICAM-1) on thyroid cancer. AIC100
cells also express the transmembrane domain of CD8 alpha and intracellular domains of the
co-stimulatory receptors CD28 and 41BB, and the cytoplasmic signaling domain of the T cell
receptor associated CD3. In addition, AIC100 cells express the somatostatin receptor subtype
2 (SSTR2), which should enable CAR T cell imaging in the patient.
The treatment with AIC100 is a single dose infusion. However, additional infusions may be
administered if the following conditions are met: (1) patient shows stable disease or partial
response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after 30 days, (2)
the investigator has deemed it is in the best interest of the patient, (3) patient did not
experience a dose limiting toxicity (DLT), and (4) there are cell doses available from the
already manufactured cell product. The cell dose for subsequent infusions will be similar to
that of the initial dose. In individual cases and only with the explicit approval of the Data
and Safety Monitoring Board (DSMB) and Food and Drug Administration (FDA), a higher dose
could be administered. This would typically be justified by efficacy and toxicity data
generated in other participants. Prior to additional infusions, lymphodepleting chemotherapy
will be repeated.
Enrollment will be staggered so that each patient will be followed for at least 30 days prior
to enrollment of the next patient for the initial Dose 1 cohort. This is a dose escalation
study using cohorts of 3 patients. Patients will receive a flat dose of 1 x 10e7, 1 x 10e8 or
5 x 10e8 viable CAR T cells with a dose -1 Cohort of 1 x 10e6
Inclusion Criteria:
1. Willing and able to participate in the study and provide written informed consent.
2. One of the following thyroid malignancies:
1. Anaplastic Thyroid Cancer (ATC), BRAF wild-type at any stage including newly
diagnosed.
2. Anaplastic Thyroid Cancer (ATC) BRAF mutant after failure of BRAF specific
therapy.
3. Poorly differentiated thyroid cancer that has failed surgery, radioactive iodine,
chemotherapy, radiation therapy and/or targeted therapies.
3. Measurable disease (by Computed Tomography [CT] scan or Positron Emission
Tomography/Computed Tomography [PET/CT])
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
5. Life expectancy of greater than 8 weeks.
6. Adequate hepatic, renal, bone marrow, and coagulation function defined as:
1. Estimated creatinine clearance >= 60 ml/min
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x the
upper limit of normal (ULN); subjects with hepatic metastases ALT and AST <= 3.0
x ULN
3. Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome,
then serum bilirubin <= 3 mg/dL
4. Serum albumin >= 3.0 g/dL
7. Has recovered by toxicity or prior anticancer therapy to Grade 0-1
8. Absolute lymphocyte count (ALC) >= 300/mm3 prior to apheresis
9. 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.
10. Females of reproductive potential must have a negative serum beta human chorionic
gonadotropin pregnancy test result at screening and within 48 hours prior to the first
dose of study therapy.
11. Detectable ICAM 1 expression on tumor by immunohistochemistry
Exclusion Criteria:
1. Women who are pregnant or breastfeeding.
2. Active systemic infections that are not controlled.
3. Previous treatment with investigational gene therapy or chimeric antigen receptor
therapy.
4. Presence of active and clinically relevant central nervous system disorder such as
epilepsy, stroke.
5. Evidence of another malignancy within 2 years prior to Screening (except in situ non-
melanoma skin cell cancers)
6. Patients with seropositive response of human immunodeficiency virus (HIV) or
uncontrolled hepatitis B virus or hepatitis C virus infections.
7. Active autoimmune disease (including but not limited to: systemic lupus erythematous,
Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory
bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to
eligibility confirmation by investigator, with the exception of thyroid replacement.
8. Patients with severe chronic diseases of kidney, liver, heart, lung. Patients with any
other serious illnesses that the investigators consider it 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 and so on.
9. Patients who need long-term use of systemic steroids.
10. Allergy to any of the chemotherapy drugs given during lymphodepletion.
