AIC100 CAR T Cells for Thyroid Cancer

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

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using modified immune cells to fight certain types of thyroid cancer that haven't responded to other treatments. The patient's own cells are changed in a lab to better target and kill cancer cells, then reintroduced into their body. This new method aims to improve the ability of the patient's immune system to find and destroy cancer cells.

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.

What safety data exists for AIC100 CAR T Cells in humans?

CAR T cell therapy, including treatments like AIC100, can have side effects such as thyroid inflammation (thyroiditis), as seen in some patients with other conditions. However, reports of severe immune-related reactions are rare, and more research is needed to fully understand the safety profile. ^{1 2 3 4 5}

How is the AIC100 CAR T Cells treatment different from other treatments for thyroid cancer?

AIC100 CAR T Cells treatment is unique because it uses genetically modified immune cells (CAR T cells) to specifically target and kill thyroid cancer cells that express a protein called ICAM-1, which is often found in aggressive thyroid cancers. This approach is different from traditional treatments as it offers a targeted and potentially more effective option for cancers with limited treatment choices. ^{2 6 7 8 9}

What data supports the effectiveness of the AIC100 CAR T Cells treatment for thyroid cancer?

Research shows that CAR T cells targeting ICAM-1 can effectively kill thyroid cancer cells in lab studies and animal models, leading to long-term remission and improved survival in mice with advanced thyroid cancer. ^{2 6 7 10 11}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Characterization of the Immune Cell Infiltration Landscape of Thyroid Cancer for Improved Immunotherapy. [2021]

2. Switzerland 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Old and new insights in the treatment of thyroid carcinoma. [2021]

4. Egypt pubmed.ncbi.nlm.nih.gov

Advances in cellular therapy for the treatment of thyroid cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Reduced Tumor Size of Untreated Papillary Thyroid Carcinoma After Immune Checkpoint Inhibitor-Induced Thyroiditis. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Hashimoto's thyroiditis after CD19 chimeric antigen receptor T-cell therapy. [2022]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Current and future immunotherapies for thyroid cancer. [2018]

10. Greece pubmed.ncbi.nlm.nih.gov

Thyroid tumor-initiating cells: increasing evidence and opportunities for anticancer therapy (review). [2021]

11. Thailand pubmed.ncbi.nlm.nih.gov

Targeting the BRAF Signaling Pathway in CD133pos Cancer Stem Cells of Anaplastic Thyroid Carcinoma [2019]