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

NCT ID: NCT06868433

Last Updated: 2025-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-08

Study Completion Date

2027-01-31

Brief Summary

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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.

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Detailed Description

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PRIMARY OBJECTIVE:

I. To determine the safety, tolerability, and recommended dose and schedule of TMV vaccine alone or TMV vaccine plus pembrolizumab in patients with surgically resected, recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC).

SECONDARY OBJECTIVE:

I. To assess vaccine-induce immune activity, antitumor response, progression-free survival (PFS) and overall survival (OS) in adult patients with recurrent and/or metastatic HNSCC administered TMV vaccine alone and TMV vaccine plus pembrolizumab.

TERTIARY/EXPLORATORY OBJECTIVES:

I. Determine whether TMV vaccine induces immune response and the magnitude of the response.

II. Next-generation sequencing (NGS) will be performed using patients' tumor samples and peripheral blood mononuclear cells to assess tumor mutational burden and identify potential neoantigens.

OUTLINE: This is a dose-escalation study of TMV vaccine alone and in combination with (fixed-dose) pembrolizumab. Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) on study.

COHORT 2: Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients also receive pembrolizumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional CT, MRI or PET on study.

After completion of study treatment, patients are followed up on day 90 then every 3 weeks for up to 12 months.

Conditions

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Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Metastatic Head and Neck Squamous Cell Carcinoma Metastatic Hypopharyngeal Squamous Cell Carcinoma Metastatic Laryngeal Squamous Cell Carcinoma Metastatic Nasopharyngeal Squamous Cell Carcinoma Metastatic Oral Cavity Squamous Cell Carcinoma Metastatic Oropharyngeal Squamous Cell Carcinoma Metastatic Sinonasal Squamous Cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Nasopharyngeal Squamous Cell Carcinoma Recurrent Oral Cavity Squamous Cell Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma Recurrent Sinonasal Squamous Cell Carcinoma Squamous Cell Carcinoma of Unknown Primary Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8 Stage IV Hypopharyngeal Carcinoma AJCC v8 Stage IV Laryngeal Cancer AJCC v8 Stage IV Lip and Oral Cavity Cancer AJCC v8 Stage IV Nasopharyngeal Carcinoma AJCC v8 Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IV Sinonasal Cancer AJCC v8

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (TMV vaccine therapy)

Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional CT, MRI or PET on study.

Group Type EXPERIMENTAL

Autologous Tumor Membrane Vesicles Vaccine

Intervention Type BIOLOGICAL

Given intradermally

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Echocardiography

Intervention Type PROCEDURE

Undergo echocardiography

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Surgical Procedure

Intervention Type PROCEDURE

Provide tissue from standard of care surgery

Cohort 2 (TMV vaccine therapy, pembrolizumab)

Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients also receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional CT, MRI or PET on study.

Group Type EXPERIMENTAL

Autologous Tumor Membrane Vesicles Vaccine

Intervention Type BIOLOGICAL

Given intradermally

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Echocardiography

Intervention Type PROCEDURE

Undergo echocardiography

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Surgical Procedure

Intervention Type PROCEDURE

Provide tissue from standard of care surgery

Interventions

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Autologous Tumor Membrane Vesicles Vaccine

Given intradermally

Intervention Type BIOLOGICAL

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Echocardiography

Undergo echocardiography

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Surgical Procedure

Provide tissue from standard of care surgery

Intervention Type PROCEDURE

Other Intervention Names

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Autologous TDMV-derived Vaccine Autologous TMV Vaccine Autologous TMV-based Vaccine Autologous Tumor-derived Membrane Vesicles Vaccine Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography EC Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI BCD-201 GME 751 GME751 Keytruda Lambrolizumab MK 3475 MK-3475 MK3475 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 QL2107 RPH 075 RPH-075 RPH075 SCH 900475 SCH-900475 SCH900475 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

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Inclusion Criteria

* 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)
* Recurrent and/or metastatic HNSCC that has failed standard chemotherapy and immunotherapy. Eligible subjects must have progressed on ≥ 2 lines of standard of care prior to starting trial therapy. For patients who have relapsed within 6 months of systemic therapy given with curative intent, that therapy will count as a line of metastatic therapy. Eligible subjects will have no restriction on prior lines of therapy in the metastatic/advanced disease setting
* The tumors should be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* Must have enough tissue collected after salvage surgery to make at least 3 doses of vaccine (minimum weight of the resectable tumor tissue is ≥ .5 grams) and adequate cellularity (\> 40% cellularity) assessed by the head and neck pathologists
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Absolute neutrophil count ≥ 1,500 cells/uL
* Platelets ≥ 100,000/uL
* Hemoglobin ≥ 9.0g/dL (may receive packed red blood cell \[prbc\] transfusion)
* Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Albumin ≥ 3.0 g/dL
* Serum creatinine ≤ 1.5 x ULN
* Calculated creatinine clearance of ≥ 50 mL/min
* International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving low molecular weight (LMW) heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level \< 1.1U/mL are allowed on the trial
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
* Ability to understand and willingness to sign written informed consent documents
* Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion
* Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion
* Female subjects of childbearing age must have a negative serum pregnancy test at study entry
* Patients who have received prior pembrolizumab are eligible

Exclusion Criteria

* 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
* Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* Women who are pregnant or lactating, and child-bearing potential women without adequate contraception
* Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
* Clinical evidence of bleeding diathesis or coagulopathy
* Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for \> 5 years. Patients with prior in situ carcinomas are eligible provided there was complete removal
* Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment
* Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
* History of severe hypersensitivity reactions to other monoclonal antibodies
* Non-oncology vaccines within 28 days prior to planned treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Dong Shin

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong M. Shin, MD, FACP, FAAAS

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Dong M. Shin, MD, FACP, FAAAS

Role: CONTACT

404-778-2980

Facility Contacts

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Madison Stallings

Role: primary

404-686-1794

Madison Stallings

Role: primary

404-686-1794

Other Identifiers

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NCI-2024-08422

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00006705

Identifier Type: OTHER

Identifier Source: secondary_id

Winship6045-23

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01CA262123-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00006705

Identifier Type: -

Identifier Source: org_study_id

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