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TMV Vaccine Therapy Alone and With Pembrolizumab for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer

ConditionsClinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Metastatic Head and Neck Squamous Cell CarcinomaMetastatic Hypopharyngeal Squamous Cell CarcinomaMetastatic Laryngeal Squamous Cell CarcinomaMetastatic Nasopharyngeal Squamous Cell CarcinomaMetastatic Oral Cavity Squamous Cell CarcinomaMetastatic Oropharyngeal Squamous Cell CarcinomaMetastatic Sinonasal Squamous Cell CarcinomaRecurrent Head and Neck Squamous Cell CarcinomaRecurrent Hypopharyngeal Squamous Cell CarcinomaRecurrent Laryngeal Squamous Cell CarcinomaRecurrent Nasopharyngeal Squamous Cell CarcinomaRecurrent Oral Cavity Squamous Cell CarcinomaRecurrent Oropharyngeal Squamous Cell CarcinomaRecurrent Sinonasal Squamous Cell CarcinomaSquamous Cell Carcinoma of Unknown PrimaryStage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8Stage IV Hypopharyngeal Carcinoma AJCC v8Stage IV Laryngeal Cancer AJCC v8Stage IV Lip and Oral Cavity Cancer AJCC v8Stage IV Nasopharyngeal Carcinoma AJCC v8Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IV Sinonasal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEmory University

About this trial

This phase Ib trial tests the safety, side effects and best dose of tumor membrane vesicle (TMV) vaccine therapy alone and in combination with pembrolizumab and evaluates how well it works in treating patients with head and neck squamous cell cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Vaccines made from a person's tumor cells, such as TMV vaccines, may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving TMV vaccine therapy alone or with pembrolizumab may be safe, tolerable and/or effective in treating patients with recurrent and/or metastatic head and neck squamous cell cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Must be at least ≥ 18 years of age

Histologically proven squamous cell carcinoma of the head and neck (HNSCC), amenable to salvage surgery. p16 positive and negative allowed. Squamous cell carcinoma of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, sinonasal carcinoma and cancer of unknown primary (squamous cell carcinoma only) are all allowed. They will be allowed to have up to 3 different regimens after diagnosed of recurrent or metastatic HNSCC

Oropharyngeal tumors must have p16 or human papillomavirus (HPV) testing done

The tumor tissues must be available and banked (- 80°C) at the time of salvage surgery (1st informed consent form [ICF] must be signed)

Disqualifiers

Salivary tumors and non-squamous cell histology in head and neck cancer

Not enough tissue collected after surgery for a planned 3 doses (weight of the resectable tumor tissue is less than 1.0 gram)

Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)

Prior organ allograft or allogeneic bone marrow transplantation

Trial design

Design model

Parallel

Treatments tested in this trial

  • Autologous Tumor Membrane Vesicles Vaccine

    Biological/Vaccine

    Given intradermally

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography

    Procedure/Surgery

    Undergo echocardiography

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET

  • Surgical Procedure

    Procedure/Surgery

    Provide tissue from standard of care surgery

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Cohort 1 (TMV vaccine therapy)Experimental treatment 7 interventions
Group B: Cohort 2 (TMV vaccine therapy, pembrolizumab)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Dose-limiting toxicity (DLT)

DLT will be defined as treatment-related adverse event that is hematologic grade 4 or non-hematologic of grade 3 or higher severity using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. DLTs will be summarized as frequency and percentage by dose levels for cohort 1 and 2 separately.

Time frame
From first dose of treatment up to 7 weeks
2

Incidence of treatment-emergent adverse events (TEAE)

Adverse events will be assessed and graded according to NCI CTCAE v 5.0. TEAEs will be summarized based on the number (percentage) of patients experiencing events. Summaries of treatment-related TEAEs, grade 3 or higher TEAEs, serious TEAEs, and TEAEs leading to discontinuation of study drug will be provided. TEAEs and the treatment-related TEAEs will also be summarized by severity.

Time frame
Up to 30 days after last dose of treatment
3

Recommended phase 2 dose (RP2D)

Will be determined by the principal investigator based upon all available safety and immune response data by dose levels from both cohorts 1 and 2. The RP2D may not exceed the maximum tolerated dose as estimated in cohort 2.

Time frame
Up to 7 weeks

Secondary outcomes

1

Vaccine-induced immune response

Response will be defined as the fold-change of IFNg+CD4/CD8 T cells by fluorescence activated cell sorting from peripheral blood before and after each vaccination. Summary statistics (mean, median, quartile \[Q\]1-Q3) will be used to describe it by dose level and time points.

Time frame
Before and after each vaccination up to 6 weeks
2

Tumor response rate

Will be assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. Tumor response will be summarized descriptively using frequencies and percentages. Response rate will be calculated as proportion along with 95% confidence intervals using the Clopper-Pearson method.

Time frame
Up to 12 months
3

Progression-free survival (PFS)

PFS rates will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test.

Time frame
From start of treatment to time of progression or death up to 12 months
4

Overall survival (OS)

OS rates will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test.

Time frame
From start of treatment to time of death up to 12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Emory University

Lead sponsor

National Cancer Institute (NCI)

Collaborator

National Institutes of Health (NIH)

Collaborator

Source ClinicalTrials.gov
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