AIC100 CAR T Cells for Thyroid Cancer

Not currently recruiting at 3 trial locations

Overseen By Sonal Gupta, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AffyImmune Therapeutics, Inc.

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AIC100 CAR T cells, a type of immunotherapy, for individuals with hard-to-treat thyroid cancers, including poorly differentiated and anaplastic thyroid cancers. The main goal is to determine the treatment's safety and identify the best dose for future studies. Multiple groups in the trial receive different treatment amounts to find the most effective dose. This trial suits individuals who have not found success with other thyroid cancer treatments such as surgery, radiation, or chemotherapy. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement to meet the minimum washout time for previous cancer treatments before certain procedures, so it's best to discuss your specific medications with the study team.

Is there any evidence suggesting that AIC100 CAR T Cells are likely to be safe for humans?

Research has shown that AIC100 CAR T cells are safe for humans. In earlier studies, researchers tested AIC100 in patients with thyroid cancer that had returned or resisted other treatments. These studies found the treatment to be generally well-tolerated, with no major safety issues, and it showed promising results in fighting tumors. Specifically, the treatment did not cause any serious or unexpected problems for the patients who received it. Overall, the data suggest that AIC100 is a safe option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for thyroid cancer, which typically involve surgery, radioactive iodine therapy, and thyroid hormone therapy, AIC100 CAR T Cells represent a novel approach by harnessing the body's immune system to fight cancer. Most current treatments target the thyroid gland itself, but AIC100 CAR T Cells work differently by genetically engineering patients' T cells to specifically recognize and attack cancer cells. This targeted approach not only has the potential to enhance treatment efficacy but also reduce side effects compared to more traditional therapies. Researchers are excited about the potential of AIC100 CAR T Cells to offer a more personalized and precise treatment option for thyroid cancer patients.

What evidence suggests that AIC100 CAR T Cells might be an effective treatment for thyroid cancer?

Research shows that AIC100 CAR T cells may help treat advanced thyroid cancers. This trial will administer different dose levels of AIC100 CAR T cells to evaluate safety and efficacy. One study found this treatment to be safe and showed promising results in fighting tumors. Specifically, at certain dose levels, 22% of patients experienced significant tumor shrinkage, and 56% managed to keep their disease under control. The treatment targets ICAM-1, a protein on cancer cells, and aids the immune system in attacking these cells. Overall, early studies suggest AIC100 could be effective for patients whose thyroid cancer has returned or is not responding to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Sonal Gupta, MD PhD

Principal Investigator

AffyImmune Therapeutics, Inc.

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory poorly differentiated thyroid cancer or anaplastic thyroid cancer, who have measurable disease and are in relatively good health. Participants must not be pregnant, breastfeeding, or on certain immunosuppressants. They should not have had gene therapy before and must agree to use effective contraception.

Inclusion Criteria

My liver, kidneys, heart, blood, and bone marrow are all working well.

Women who could become pregnant must have a negative pregnancy test.

My thyroid cancer tests positive for ICAM-1.

Exclusion Criteria

I am not allergic to chemotherapy drugs or any components of AIC100 CAR T Cells.

I do not have severe chronic diseases like kidney, liver, heart, or lung conditions.

I have not had gene or CAR T cell therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and CAR T Cell Preparation

Patients undergo apheresis for collection of autologous lymphocytes, which are then transfected and expanded in vitro to generate the AIC100 CAR T Cell product

3-4 weeks

Lymphodepleting Chemotherapy

Patients receive lymphodepleting chemotherapy prior to CAR T cell infusion

1 week

Treatment

Infusion of AIC100 CAR T Cells at various dose levels

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for adverse events and persistence of CAR T cells

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• AIC100 CAR T Cells

Trial Overview The trial is testing AIC100 CAR T Cells for safety and tolerability to find the best dose for Phase 2 trials in patients with specific types of advanced thyroid cancer that haven't responded well to other treatments.

How Is the Trial Designed?

Group I: Cohort 5 Experimental Treatment 1 Intervention

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.

Group II: Cohort 4 Experimental Treatment 1 Intervention

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.

Group III: Cohort 3 Experimental Treatment 1 Intervention

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

Group IV: Cohort 2.5 Experimental Treatment 1 Intervention

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.

Group V: Cohort 2 Experimental Treatment 1 Intervention

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

Group VI: Cohort 1 Experimental Treatment 1 Intervention

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

Group VII: Cohort -1 Experimental Treatment 1 Intervention

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

AIC100 CAR T Cells is already approved in United States for the following indications:

Approved in United States as AIC100 CAR T Cells for:

• Anaplastic thyroid cancer
• Refractory poorly differentiated thyroid cancer

Who Is Running the Clinical Trial?

AffyImmune Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

Thyroid cancer is believed to be initiated by tumor-initiating cells (TICs), which contribute to the cancer's progression, resistance to treatment, and recurrence.

Current research is focused on identifying effective therapeutic strategies to target these TICs, which have been isolated using specific biomarkers and assays, but their characteristics and how to effectively treat them remain challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid tumor-initiating cells: increasing evidence and opportunities for anticancer therapy (review). Gao, YJ., Li, B., Wu, XY., et al.[2021]

Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have shown overall survival benefits in cancer patients, with response rates between 20% and 40%, indicating their potential effectiveness across various cancers, including thyroid cancer.

Recent studies suggest that targeting cytokines and chemokines in the tumor microenvironment may provide therapeutic benefits in thyroid cancer, with promising results seen in a case of anaplastic thyroid cancer treated with nivolumab, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future immunotherapies for thyroid cancer. Antonelli, A., Ferrari, SM., Fallahi, P.[2018]

A 49-year-old man with metastatic colon cancer developed CPI-induced thyroiditis during treatment, which led to a significant regression of his untreated primary papillary thyroid carcinoma (PTC), suggesting a potential link between immune responses triggered by CPIs and tumor reduction.

After starting treatment with the CPI ezabenlimab, the patient's PTC tumor size decreased by 60.7% over one year, indicating that CPI-induced thyroiditis may enhance immune activity against PTC cells, warranting further investigation into this immunological mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced Tumor Size of Untreated Papillary Thyroid Carcinoma After Immune Checkpoint Inhibitor-Induced Thyroiditis. Chen, DH., Lenz, HJ., Lechner, MG., et al.[2023]

In a study of 103 patients with advanced cancer treated with combination anti-PD1/anti-CTLA4 therapies, 16.5% developed thyroid immune-related adverse events (irAEs), indicating that these side effects are relatively common and should be monitored regularly.

The occurrence of thyroid irAEs was associated with better overall survival rates, suggesting that these adverse events may have a positive prognostic significance in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes. Lui, DTW., Lee, CH., Tang, V., et al.[2022]

In a study of 46 intermediate-risk differentiated thyroid cancer patients, BRAF mutations and high AXL expression were linked to a poorer response to radioiodine therapy (RIT), suggesting these factors could help identify patients who may not benefit as much from RIT.

The research also found that higher levels of PD-L1 and lower levels of NIS expression were associated with less effective RIT responses, indicating that these biomarkers could be used to tailor treatment strategies for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF-AXL-PD-L1 Signaling Axis as a Possible Biological Marker for RAI Treatment in the Thyroid Cancer ATA Intermediate Risk Category. Pizzimenti, C., Fiorentino, V., Ieni, A., et al.[2023]

In a study of 505 thyroid cancer samples, researchers identified three immune cell infiltration (ICI) subtypes, revealing that a higher ICI score is linked to increased tumor mutation burden and better overall survival rates.

Patients with high ICI scores showed significant therapeutic benefits from immunotherapy, suggesting that ICI scores can serve as a valuable prognostic indicator for treatment response in thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the Immune Cell Infiltration Landscape of Thyroid Cancer for Improved Immunotherapy. Gong, J., Jin, B., Shang, L., et al.[2021]

Thyroid cancer is the most common endocrine tumor, with 33,550 new cases diagnosed annually and a relatively low mortality rate of 1,530 patients per year, indicating a generally favorable prognosis.

Recent advancements in treatment options for thyroid carcinoma have shown unexpectedly positive results, suggesting that new therapeutic agents may improve patient outcomes compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Old and new insights in the treatment of thyroid carcinoma. Gasent Blesa, JM., Grande Pulido, E., Provencio Pulla, M., et al.[2021]

There are currently no curative therapies for metastasized undifferentiated/anaplastic thyroid carcinomas, but immunotherapy using dendritic cells (DCs) shows promise in enhancing the body's immune response against tumors.

Dendritic cells can effectively present tumor antigens to activate cytotoxic T cells, and alternative strategies like adoptive cell transfer using natural killer cells or matured T cells are also being explored to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in cellular therapy for the treatment of thyroid cancer. Papewalis, C., Ehlers, M., Schott, M.[2022]

ICAM-1 CAR T cells effectively targeted and killed poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC) cells in vitro, demonstrating the potential for this therapy to treat aggressive thyroid cancers.

In mouse models of systemic ATC, a single dose of ICAM-1 CAR T cells led to significant tumor reduction, long-term remission, and improved survival, indicating a promising new treatment approach for patients with advanced thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors. Min, IM., Shevlin, E., Vedvyas, Y., et al.[2019]

Cancer stem cells (CSCs) in anaplastic thyroid carcinoma (ATC) show significantly higher expression of the BRAFV600E gene compared to normal thyroid cells, indicating their role in tumorigenesis, while the sodium-iodide symporter (NIS) gene is expressed at very low levels.

Inhibition of the BRAF pathway not only affects the expression of NIS but also its localization, suggesting that targeting CSCs and their signaling pathways could enhance treatment strategies for ATC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the BRAF Signaling Pathway in CD133pos Cancer Stem Cells of Anaplastic Thyroid Carcinoma Bozorg-Ghalati, F., Hedayati, M., Dianatpour, M., et al.[2019]

CAR-T cell therapy is effective in treating relapsed refractory diffuse large B-cell lymphoma, achieving complete remission in two patients within 1 to 3 months after treatment.

However, this therapy can lead to immune-related adverse effects, as demonstrated by two cases of Hashimoto's thyroiditis, indicating a need for further investigation into the mechanisms behind thyroid inflammation following CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Hashimoto's thyroiditis after CD19 chimeric antigen receptor T-cell therapy. Chen, P., Xia, Y., Lei, W., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6112

Safety and efficacy of AIC100 chimeric antigen receptor ... This first-in-human ICAM-1 targeted CAR T-cell study demonstrated an excellent safety profile and promising antitumor activity for AIC100 in patients with PDTC ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04420754

NCT04420754 | Study of AIC100 CAR T Cells in Relapsed ... 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 ...

3. ascopost.com ascopost.com/news/may-2025/novel-car-t-cell-therapy-induces-response-in-patients-with-advanced-thyroid-cancers/

AACR 2025: Novel CAR T-Cell Therapy Induces Response ... For nine patients receiving dose level 2 or 3, 22% were observed to have significant tumor shrinkage and 56% had control of their disease. “The ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT206/761746/Abstract-CT206-ICAM-1-directed-chimeric-antigen

Abstract CT206: ICAM-1 directed chimeric antigen receptor ... AIC100, a first-in-human ICAM-1 directed CAR T-cell therapy, demonstrated an acceptable safety profile in patients with relapsed/refractory ATC ...

5. cancernetwork.com cancernetwork.com/view/novel-car-t-cell-therapy-receives-fda-rmat-status-in-advanced-thyroid-cancer

Novel CAR T-Cell Therapy Receives FDA RMAT Status in ... The objective response rate (ORR) for all patients was 22% and. There was 1 partial response in a patient with anaplastic thyroid cancer at dose ...