Study of AIC100 CAR T Cells in Relapsed/Refractory Thyroid Cancer

NCT04420754 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-12021154
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to assess the safety and tolerability and determine the recommended Phase 2 dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer, including newly diagnosed.

Conditions

Anaplastic Thyroid Cancer; Relapsed/Refractory Poorly Differentiated Thyroid Cancer

Keywords

AIC100; CAR T Cell; Anaplastic Thyroid Cancer; Poorly Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of overall Grade >=3 Adverse Events (AE) and Serious Adverse Events (SAE)

  The number of Grade 3, 4 and 5 AEs and SAEs that occur throughout the study.

  Up to 1 year post-infusion

• Incidence of anticipated AIC100 CAR T Cell related AEs, SAEs and adverse events of special interest (AESI) (infusion-related reactions, CRS, ICANS, HLH/MAS, TLS, new malignancies, AEs leading to death and DLT AEs)

  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 new malignancies.

  Up to 15 years post-infusion

• Determine recommended phase 2 dose

  The recommended phase 2 dose will be determined through the dose escalation process

  Up to 1 year post infusion

Secondary Outcomes (1)

• Assessment of presence and frequency of AIC100 CAR T cells in peripheral blood and tumor samples (when available)

  Up to 15 years post-infusion

Study Arms (7)

Cohort -1

EXPERIMENTAL

AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells

Biological: AIC100 CAR T Cells

Cohort 1

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells

Biological: AIC100 CAR T Cells

Cohort 2

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells

Biological: AIC100 CAR T Cells

Cohort 3

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells

Biological: AIC100 CAR T Cells

Cohort 2.5

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 2.5 (Flat Dose): 2.5 x 10e8 CAR T cells. The interim step-down dose of Cohort 2.5 may be evaluated, if needed, based on ongoing safety and efficacy data.

Biological: AIC100 CAR T Cells

Cohort 4

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 4 (Flat Dose): 7.5 x 10e8 CAR T cells. The proposed escalation dose of Cohort 4 may be evaluated, if needed, based on ongoing safety and efficacy data.

Biological: AIC100 CAR T Cells

Cohort 5

EXPERIMENTAL

AIC100 CAR T Cell Dose Level 5 (Flat Dose): 1 x 10e9 CAR T cells. The proposed escalation dose of Cohort 5 may be evaluated, if needed, based on ongoing safety and efficacy data.

Biological: AIC100 CAR T Cells

Interventions

AIC100 CAR T Cells BIOLOGICAL

Autologous CAR T cells directed against ICAM-1

Also known as: AIC100

Cohort -1; Cohort 1; Cohort 2; Cohort 2.5; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to participate in the study and provide written informed consent
• Be ≥ 18 years of age on the day of signing the Informed Consent Form
• Patients must have thyroid cancer that meets one of the following diagnoses, and, prior to lymphodepleting chemotherapy (LDC), have an identified available fresh or archival biopsy sample:
• Anaplastic Thyroid Cancer BRAF wild-type at any stage, including newly diagnosed
• Anaplastic Thyroid Cancer BRAF mutant after failure of or inability to tolerate BRAF- specific therapy
• Poorly Differentiated Thyroid Cancer that has failed any of the following treatments: surgery radioactive iodine, chemotherapy, radiation therapy, and/or targeted therapies
• Measurable disease by Computed Tomography (CT) or Positron Emission Tomography (PET) PET/CT per RECIST v1.1
• a. For ATC patients who do not have measurable disease at Screening, they are required to have measurable disease at Baseline Day -7 to proceed in the study.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Life expectancy greater than 8 weeks
• Overall adequate hepatic, renal, bone marrow, cardiac, and coagulation function, defined as the following:
• Estimated creatinine clearance ≥ 50 mL/minute
• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): normal or Grade 1. Note: Lymphodepleting Chemotherapy (LDC) agents can cause fluctuations in hepatic enzymes.
• Serum total bilirubin: normal or Grade 1. Note: LDC agents can cause fluctuations in hepatic enzymes.
• Serum albumin: normal or Grade 1. (human albumin supplementation is not allowed within 2 weeks prior to Screening assessment)

You may not qualify if:

• Women who are pregnant or breastfeeding
• Patients with Human immunodeficiency virus (HIV) must have been on effective antiretroviral therapy for ≥ 4 weeks prior to enrollment; must have an HIV viral load \< 400 copies/µL; no acquired immunodeficiency syndrome related opportunistic infections in the previous 12 months; and a CD4+ cell count ≥ 350 cells/µL
• Patients with chronic hepatitis B virus (HBV) infection must be on antiviral therapy and have an HBV viral load below the limits of detection
• Patients with chronic hepatitis C virus (HCV) infection must have completed therapy and have an HCV viral load below the limits of detection
• Prior treatment with investigational gene therapy or CAR T cell therapy
• Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke, or symptomatic or uncontrolled brain metastases
• Evidence of another malignancy within 2 years prior to Screening (except in-situ non melanoma skin cancers, localized controlled prostate cancer, adequately treated Stage 1 uterine cancer that has a low risk of recurrence, or any other malignancies with similar outcome)
• Active autoimmune disease (including but not limited to systemic lupus erythematosus, Sjögren's Syndrome, rheumatoid arthritis (RA), psoriasis, multiple sclerosis, inflammatory bowel disease) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation
• Patients with severe chronic diseases of the kidney, liver, heart, lung; or any other serious illness that, in the opinion of the Investigator, may affect the patient's treatment, follow up, or assessments, including but not limited to uncontrolled clinically significant neurological or psychiatric disorders or metabolic diseases
• Patients who need long-term use of systemic corticosteroids \> 10 mg/day prednisone or equivalent
• Allergy to the chemotherapy drugs given during lymphodepletion or known hypersensitivity to any component of AIC100 CAR T Cells, including excipients
• Receipt of a COVID-19 vaccine within 4 weeks before Screening
• Concurrent participation in another interventional clinical study during participation in this study
• Prior treatment with any gene therapy or genetically modified cell therapy, including CAR T cells
• Prior treatment with ICAM-1 directed antibody, bispecific T cell engager, or antibody drug conjugate, unless there is confirmed ICAM-1 expression (by immunohistochemistry) after progression or relapse following most recent ICAM-1 directed treatment.

Sponsors & Collaborators

• AffyImmune Therapeutics, Inc.: lead

Study Sites (4)

City of Hope National Medical Center, City of Hope Medical Center

Duarte, California, 91010, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic; Recurrence

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sonal Gupta, MD PhD

  AffyImmune Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 9, 2020
• Study Start: September 28, 2020
• Primary Completion (Estimated): August 4, 2026
• Study Completion (Estimated): August 4, 2030
• Last Updated: March 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)