Study of AIC100 in Relapsed/Refractory Thyroid Cancer

Sponsor

AffyImmune Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04420754

Collaborator

(none)

Enrollment

Locations

Arms

45.1

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Thyroid Cancer Relapsed/Refractory Poorly Differentiated Thyroid Cancer	Biological: AIC100 CAR T Cells	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi Center Phase I Study of AIC100 in Relapsed and/or Refractory Advanced Thyroid Cancer and Anaplastic Thyroid Cancer

Actual Study Start Date :

Sep 28, 2020

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort -1 AIC100 Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells	Biological: AIC100 CAR T Cells Autologous CAR T cells directed against ICAM-1 Other Names: AIC100
Experimental: Cohort 1 AIC100 Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells	Biological: AIC100 CAR T Cells Autologous CAR T cells directed against ICAM-1 Other Names: AIC100
Experimental: Cohort 2 AIC100 Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells	Biological: AIC100 CAR T Cells Autologous CAR T cells directed against ICAM-1 Other Names: AIC100
Experimental: Cohort 3 AIC100 Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR Tcells	Biological: AIC100 CAR T Cells Autologous CAR T cells directed against ICAM-1 Other Names: AIC100

Outcome Measures

Primary Outcome Measures

Incidence of overall Grade 3 - 5 Adverse Events (AE) [42 days post-infusion]
The number of Grade 3, 4 and 5 adverse events that occur throughout the study, both serious and non-serious and related and not related.
Incidence of CAR T-related AEs or adverse events of special interest (AESI) [42 days post-infusion]
The number of CAR T related adverse events that occur throughout the study, including AESIs (infusion-related reactions, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), tumor lysis syndrome (TLS) and genotoxicity).

Secondary Outcome Measures

Detection, Expansion and Persistence of AIC100 cells after infusion [Up to 15 years post-infusion]
Number of AIC100 cells present after infusion by polymerase chain reaction (PCR)
Analysis of CAR T Subsets by Flow Cytometry in Peripheral Blood [Up to 15 years post-infusion]
Measurement of CAR T cell subsets by flow cytometry in peripheral blood
Assessment and Analysis of CAR T cell infiltrate in tumor by biopsy [42 days post-infusion]
Comparison of tumor biopsies collected prior to initiation of AIC100 therapy and at the end of treatment and/or progression to assess cellular infiltrate and immune profiling.
Cytokine levels in plasma samples [42 days post-infusion]
Measurement of cytokine levels in plasma samples by enzyme-linked immunosorbent assay (ELISA) to evaluate correlation with CAR T levels and with clinical tumor response
CAR T Antibodies in peripheral blood [Up to 15 years post-infusion]
Assessment and measurement of CAR T antibodies in peripheral blood post-infusion

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.