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

• ClinicalTrials.gov Identifier: NCT04420754
• Recruitment Status: Recruiting
• First Posted: June 9, 2020
• Last Update Posted: November 13, 2023
• Sponsor: AffyImmune Therapeutics, Inc.
• Information provided by (Responsible Party): AffyImmune Therapeutics, Inc.

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 9, 2020
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: September 28, 2020
• Estimated Primary Completion Date: June 28, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2023)

• Incidence of overall Grade >=3 Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to 15 years post-infusion ]
  The number of Grade 3, 4 and 5 AEs and SAEs that occur throughout the study.
• Incidence of anticipated AIC100 CAR T Cell related AEs, SAEs and adverse events of special interest (AESI) [ Time Frame: Up to 15 years 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 new malignancies.
• Determine recommended phase 2 dose [ Time Frame: Up to 15 years post-infusion ]
  The recommended phase 2 dose will be determined through the dose escalation process

Original Primary Outcome Measures (submitted: June 3, 2020)

• Incidence of overall Grade 3 - 5 Adverse Events [ Time Frame: 42 days post-infusion ]
  The number of Grade 3, 4 and 5 adverse events that occur throughout the study.
• Incidence of CAR T-related Adverse Effects [ Time Frame: 42 days post-infusion ]
  The number of CAR T related adverse effects that occur throughout the study, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) and tumor lysis syndrome (TLS)

Current Secondary Outcome Measures (submitted: August 16, 2023)

Assessment of presence and frequency of AIC100 CAR T cells in peripheral blood and tumor samples (when available) [ Time Frame: Up to 15 years post-infusion ]

Patients will be monitored for expansion and persistence of AIC100 CAR transgenes after infusion by vector copy number (VCN) analysis

Original Secondary Outcome Measures (submitted: June 3, 2020)

• Detection, Expansion and Persistence of AIC100 cells after infusion [ Time Frame: 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 [ Time Frame: Up to 15 years post-infusion ]
  Measurement of CAR T cell subsets by flow cytometry in peripheral blood
• Assessment and Analysis of CART cell infiltrate in tumor by biopsy at completion of treatment and/or progression. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 15 years post-infusion ]
  Assessment and measurement of CAR T antibodies in peripheral blood post-infusion

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of AIC100 CAR T Cells in Relapsed/Refractory Thyroid Cancer
• Official Title: A Multicenter Phase I Study of AIC100 CAR T Cells in Relapsed and/or Refractory Advanced Thyroid Cancer or Anaplastic Thyroid Cancer
• 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.

Detailed Description

The primary objective of this study is to assess the safety and tolerability of AIC100 CAR T Cells and determine the recommended Phase 2 dose of AIC100 in patients with relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic thyroid cancer that are BRAF wild-type, including newly diagnosed, 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 CAR T Cell product. After lymphodepleting chemotherapy, AIC100 CAR T Cells will be infused.

The study drug product, 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 imaging of AIC100 CAR T Cells.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Anaplastic Thyroid Cancer
• Relapsed/Refractory Poorly Differentiated Thyroid Cancer

Intervention

Biological: AIC100 CAR T Cells

Autologous CAR T cells directed against ICAM-1

Other Name: AIC100

Study Arms

• Experimental: Cohort -1
  AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells
  Intervention: Biological: AIC100 CAR T Cells
• Experimental: Cohort 1
  AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells
  Intervention: Biological: AIC100 CAR T Cells
• Experimental: Cohort 2
  AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells
  Intervention: Biological: AIC100 CAR T Cells
• Experimental: Cohort 3
  AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells
  Intervention: Biological: AIC100 CAR T Cells
• Experimental: Cohort 2.5
  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.
  Intervention: Biological: AIC100 CAR T Cells
• Experimental: Cohort 4
  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.
  Intervention: Biological: AIC100 CAR T Cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 16, 2023): 30
• Original Estimated Enrollment (submitted: June 3, 2020): 24
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: June 28, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Willing and able to participate in the study and provide written informed consent
2. Be ≥ 18 years of age on the day of signing the Informed Consent Form

3. Patients must have thyroid cancer that expresses ICAM-1 and that meets one of the following diagnoses:

   1. Anaplastic Thyroid Cancer BRAF wild-type at any stage, including newly diagnosed
   2. Anaplastic Thyroid Cancer BRAF mutant after failure of or inability to tolerate BRAF- specific therapy
   3. Poorly Differentiated Thyroid Cancer that has failed any of the following treatments: surgery radioactive iodine, chemotherapy, radiation therapy, and/or targeted therapies

4. 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.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
6. Life expectancy greater than 8 weeks

7. Overall adequate hepatic, renal, bone marrow, cardiac, and coagulation function, defined as the following:

   1. Estimated creatinine clearance ≥ 50 mL/minute
   2. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): normal or Grade 1. Note: Lymphodepleting Chemotherapy (LDC) agents can cause fluctuations in hepatic enzymes.
   3. Serum total bilirubin: normal or Grade 1. Note: LDC agents can cause fluctuations in hepatic enzymes.
   4. Serum albumin: normal or Grade 1. (human albumin supplementation is not allowed within 2 weeks prior to Screening assessment)
   5. Hemodynamically stable and left ventricular ejection fraction ≥ 45%
   6. Hematological parameters

   i. Absolute neutrophil count > 1000/μL without myeloid growth factor support for ≥ 2 weeks

   ii. Absolute lymphocyte count ≥ 100/μL at screening and at apheresis

   iii. Platelet count ≥ 50 × 1000/μL without platelet transfusion for ≥ 2 weeks

   iv. Hemoglobin concentration > 8 g/dL without red blood cell transfusion for ≥ 2 weeks

8. Has met the minimum washout time for previous cancer treatments before undergoing apheresis or LDC, and in the Investigator's judgement, the patient is able to safely undergo the procedure
9. (incorporated into inclusion criterion #7)
10. Females of reproductive potential (defined as all females physiologically capable of becoming pregnant) must agree to use 1 highly effective method of contraception and 1 additional effective method from at least 28 days before enrollment/apheresis and for at least 1 year after the infusion of AIC100 CAR T Cells.
11. Females of reproductive potential must have a negative serum beta-human chorionic gonadotropin pregnancy test result at Screening
12. (incorporated into inclusion criterion #3)

Exclusion Criteria:

1. Women who are pregnant or breastfeeding

2. Clinically significant, active, uncontrolled, systemic infection; the following are not exclusionary:

   1. Patients with 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
   2. Patients with chronic hepatitis B virus (HBV) infection must be on antiviral therapy and have an HBV viral load below the limits of detection
   3. Patients with chronic hepatitis C virus (HCV) infection must have completed therapy and have an HCV viral load below the limits of detection
3. Prior treatment with investigational gene therapy or CAR T cell therapy
4. Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke, or symptomatic or uncontrolled brain metastases
5. 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)
6. (incorporated into exclusion criterion #2)
7. 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
8. 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
9. Patients who need long-term use of systemic corticosteroids > 10 mg/day prednisone or equivalent
10. Allergy to any of the chemotherapy drugs given during lymphodepletion or known hypersensitivity to any component of AIC100 CAR T Cells, including excipients
11. Receipt of a COVID-19 vaccine within 4 weeks before Screening

12. Concurrent participation in another interventional clinical study during participation in this study

    1. Prior treatment with any gene therapy or genetically modified cell therapy, including CAR T cells
    2. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sonal Gupta, MD PhD; 508-654-3600 ext 3; sgupta@affyimmune.com

Contact: Dawn Buchanan; 508-654-3600 ext 5; dbuchanan@affyimmune.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04420754
• Other Study ID Numbers: 19-12021154
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AffyImmune Therapeutics, Inc.
• Original Responsible Party: Weill Medical College of Cornell University
• Current Study Sponsor: AffyImmune Therapeutics, Inc.
• Original Study Sponsor: Weill Medical College of Cornell University
• Collaborators: Not Provided

Investigators

• Study Director: Sonal Gupta, MD PhD; AffyImmune Therapeutics, Inc.

• PRS Account: AffyImmune Therapeutics, Inc.
• Verification Date: November 2023