Cell Therapy for Relapsed/Refractory Head and Neck Cancer

Overseen By Spencer SB Laing

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Heart disease, Stroke, Hypersensitivity, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

33 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy and cell infusion, it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment iC9.CAR-CSPG4 T cells for relapsed/refractory head and neck cancer?

The research on similar treatments, like CAR-T cells targeting other proteins in head and neck cancer, shows promising results in reducing tumor size and inhibiting growth. Additionally, the use of engineered immune cells, such as NK cells, has demonstrated effectiveness in killing cancer cells in head and neck cancer, suggesting potential for CAR-T cell therapies targeting CSPG4. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy, including treatments like iC9.CAR-CSPG4 T cells, has shown promise in treating certain cancers, but it can cause serious side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). While medical management for these side effects has improved, there is still a risk of unpredictable toxicities, especially when used for solid tumors. ^{6 7 8 9 10}

What makes the iC9.CAR-CSPG4 T cell treatment unique for head and neck cancer?

The iC9.CAR-CSPG4 T cell treatment is unique because it uses genetically engineered T cells to specifically target CSPG4, a protein often found on cancer cells, offering a personalized approach that differs from standard chemotherapy or radiation. This treatment represents a novel form of immunotherapy, potentially providing an option for patients with relapsed or refractory head and neck cancer who have limited treatment choices. ^{2 4 5 11 12}

What is the purpose of this trial?

The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen (iC9.CAR-CSPG4 T cells) in patients with head and neck cancer that came back after receiving standard therapy for this cancer. The iC9.CAR-CSPG4 treatment is experimental and has not been approved by the Food and Drug Administration. How many (dose) of the iC9.CAR. CSPG4 T cells are safe to use in patients without causing too many side effects, and what is the maximum dose that could be tolerated will be investigated. The information collected from the study would help cancer patients in the future. There are two parts to this study. In part 1, blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD). Additionally, recommended phase 2 dose will be tested. Eligible subjects will receive lymphodepletion chemotherapy standard followed by infusion of iC9-CAR.CSPG4 T cells. After treatment completion or discontinuation, subjects will be followed since involving gene transfer experiments.

Research Team

Jared Weiss, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with recurrent/metastatic squamous cell carcinoma of the head and neck, who have a Karnofsky score above 60%, indicating they can care for themselves. It's not open to those with severe heart disease, recent stroke or TIA, or allergies to cyclophosphamide or fludarabine.

Inclusion Criteria

I am mostly able to care for myself.

The subject has been provided with, and given written consent for, disclosure of their personal health information along with a HIPAA authorization form which was adequately explained to them and signed.

My cancer is a type of squamous cell carcinoma in the head or neck area.

Exclusion Criteria

I do not have severe heart problems like uncontrolled high blood pressure or recent heart attacks.

I have not had a stroke or TIA in the last year.

You have had a strong allergic reaction in the past to cyclophosphamide or fludarabine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Preparation

Blood is collected to prepare the iC9.CAR-CSPG4 T cells. Disease-fighting T cells are isolated and modified.

4 weeks

Lymphodepletion Chemotherapy

Participants receive lymphodepletion chemotherapy prior to T cell infusion.

1 week

Treatment

iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of toxicity and response rates.

Up to 2 years

Treatment Details

Interventions

• iC9.CAR-CSPG4 T cells

Trial Overview The study tests autologous CAR-T cells targeting CSPG4 in patients whose head and neck cancer returned after standard treatment. The safety and tolerable dose levels are being determined. Patients will undergo lymphodepletion chemotherapy before receiving the experimental iC9.CAR-CSPG4 T cell infusion.

Participant Groups

Group I: Chimeric Antigen Receptors Experimental Treatment 3 Interventions

blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Bellicum Pharmaceuticals

Industry Sponsor

Trials

28

Recruited

1,400+

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Collaborator

Trials

5

Recruited

150+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

High affinity natural killer cells (haNKs) can directly kill both HPV-positive and negative head and neck squamous cell carcinoma cells, showing potential as a cell therapy for tumors that evade T-cell immunity.

haNKs' effectiveness is significantly enhanced through antibody-dependent cell-mediated cytotoxicity (ADCC) when combined with treatments like cetuximab or avelumab, particularly in tumors with high EGFR or PD-L1 expression, suggesting a promising strategy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells. Friedman, J., Padget, M., Lee, J., et al.[2021]

The T4 immunotherapy, a novel CAR-T cell treatment targeting ErbB dimer expression, was safely administered intratumorally in a phase 1 trial involving patients with advanced head and neck squamous cell carcinoma, with no dose-limiting toxicities and manageable side effects.

Out of 15 subjects, 60% experienced disease stabilization six weeks after treatment, and one patient achieved a durable complete response lasting over three years, suggesting promising efficacy of this approach in a challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study. Papa, S., Adami, A., Metoudi, M., et al.[2023]

Engineered NK cells (haNKs) expressing a PD-L1 chimeric antigen receptor effectively killed head and neck cancer cells and inhibited tumor growth in both syngeneic and xenograft models, demonstrating their potential as a treatment option.

The treatment not only targeted tumors but also reduced levels of immunosuppressive myeloid cells expressing high PD-L1, suggesting that PD-L1 CAR haNKs could overcome some limitations of T cell-based therapies in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells. Robbins, Y., Greene, S., Friedman, J., et al.[2021]

PD-1 inhibitors have shown early success in treating various tumors, but in head and neck cancer, only a small percentage of patients respond, highlighting the need for more effective therapies.

Adoptive cell therapy, which uses genetically engineered T cells, holds promise for improving treatment outcomes in head and neck cancer, particularly due to the distinct biological differences between HPV-positive and HPV-negative tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Approaches Beyond PD-1 Inhibition: the Future of Cellular Therapy for Head and Neck Squamous Cell Carcinoma. Qureshi, HA., Lee, SM.[2023]

In a study involving 22 patients with head and neck squamous cell carcinoma, significant changes in immune checkpoint molecules (ICM) like PD1, BTLA, and CD27 were observed during and after radiotherapy, indicating that conventional treatment affects immune cell responses.

The research suggests potential future therapeutic strategies, such as combining radiotherapy with agonists targeting BTLA, CD137, OX40, or GITR, which could enhance the effectiveness of existing treatments like anti-PD1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC). von Witzleben, A., Fehn, A., Grages, A., et al.[2021]

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

CAR T-cell therapy has shown impressive results in treating some leukemia patients, but it struggles to effectively target common solid tumors like breast, colon, and lung cancers due to challenges such as T-cell suppression and localization issues.

Research is ongoing to improve CAR T-cell therapy for solid tumors by developing strategies to enhance T-cell function, increase their targeting accuracy, and ensure safer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy of solid tumors. Yong, CSM., Dardalhon, V., Devaud, C., et al.[2018]

CAR T-cell therapy has shown high success rates in achieving complete remission and long-term responses, particularly in advanced B-cell cancers, with FDA-approved treatments like tisagenlecleucel and axi-cel for specific leukemias and lymphomas.

The review highlights the importance of understanding CAR T-cell designs, factors influencing treatment response, and potential adverse effects, as well as exploring applications of this therapy beyond just B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current development of chimeric antigen receptor T-cell therapy. Wang, J., Hu, Y., Huang, H.[2020]

CAR T-cell therapy is a promising treatment for patients with aggressive B-cell malignancies, as it genetically modifies T-cells to specifically target and attack cancer cells.

However, this treatment can lead to severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity (ICANS), necessitating the involvement of medical emergency teams for effective management and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy and critical care : A survival guide for medical emergency teams. Messmer, AS., Que, YA., Schankin, C., et al.[2021]

CAR T cell therapies, particularly those targeting CD19, have shown significant clinical success in treating blood cancers, leading to their FDA approval.

These therapies modify the immune system to effectively recognize and attack tumor cells, offering a promising approach to overcoming drug resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy with CAR modified T cells in cancer: current landscape and future perspectives. Coscia, M., Vitale, C., Cerrano, M., et al.[2022]

T4 immunotherapy, an innovative autologous cell therapy, shows promise in treating head and neck squamous cell carcinoma (HNSCC) by genetically engineering T-cells to target cancer cells without significant toxicity, as demonstrated in preclinical models.

A first-in-man clinical trial is set to evaluate the safety and efficacy of T4(+) T-cells in patients with locally advanced/recurrent HNSCC, using a dose escalation approach to determine the maximum tolerated dose while monitoring various safety and efficacy parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. van Schalkwyk, MC., Papa, SE., Jeannon, JP., et al.[2022]

In a study of 10 patients with platinum refractory head and neck squamous cell carcinoma treated with nivolumab, only 5 patients showed stable disease or partial response, with mutations in the PI3K/AKT/PTEN pathways being common among responders.

The presence of high tumor mutational burden (TMB) in two patients correlated with long-lasting responses to immunotherapy, suggesting that genomic profiling could help identify patients more likely to benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile. Mezi, S., Pomati, G., Zizzari, IG., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells. [2021]

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

Immunotherapy Approaches Beyond PD-1 Inhibition: the Future of Cellular Therapy for Head and Neck Squamous Cell Carcinoma. [2023]

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

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC). [2021]

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

Building safety into CAR-T therapy. [2023]

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

CAR T-cell therapy of solid tumors. [2018]

8. China pubmed.ncbi.nlm.nih.gov

Current development of chimeric antigen receptor T-cell therapy. [2020]

9. Austria pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy and critical care : A survival guide for medical emergency teams. [2021]

10. Singapore pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy with CAR modified T cells in cancer: current landscape and future perspectives. [2022]

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

Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile. [2022]