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

Phase 1b Study of TMV Vaccine Therapy Alone and TMV Vaccine Plus Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; 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 Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Metastatic Hypopharyngeal Squamous Cell Carcinoma; Metastatic Laryngeal Squamous Cell Carcinoma; Metastatic Nasopharyngeal Squamous Cell Carcinoma; Metastatic Sinonasal Squamous Cell Carcinoma; Recurrent Nasopharyngeal Squamous Cell Carcinoma; Recurrent Sinonasal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Carcinoma AJCC v8; Stage IV Sinonasal Cancer AJCC v8; Metastatic Oral Cavity Squamous Cell Carcinoma; Metastatic Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Biological: Pembrolizumab; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Procedure: Echocardiography; Biological: Autologous Tumor Membrane Vesicles Vaccine; Procedure: Surgical Procedure

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dong M. Shin, MD, FACP, FAAAS; Phone Number: 404-778-2980; Email: dmshin@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Principal Investigator: Dong M. Shin, MD, FACP, FAAAS
      • Contact: Nilaab Meer; Phone Number: 404-686-1794; Email: madison.miller.stallings@emory.edu
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University Hospital Midtown
      • Principal Investigator: Dong M. Shin, MD, FACP, FAAAS
      • Contact: Nilaab Meer; Phone Number: 404-686-1794; Email: nilaab.meer@emory.edu
      • Contact: Nabil F. Saba, M.D.; Phone Number: 404-778-1900; Email: NFSABA@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Echocardiography; Undergo echocardiography; Other Names: EC; Biological: Autologous Tumor Membrane Vesicles Vaccine; Given intradermally; Other Names: Autologous TDMV-derived Vaccine; Autologous TMV Vaccine; Autologous TMV-based Vaccine; Autologous Tumor-derived Membrane Vesicles Vaccine; Procedure: Surgical Procedure; Provide tissue from standard of care surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS
Experimental: 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.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; MK3475; SCH-900475; BCD-201; Pembrolizumab Biosimilar BCD-201; Pembrolizumab Biosimilar QL2107; QL2107; GME 751; GME751; Pembrolizumab Biosimilar GME751; MK 3475; SCH900475; Pembrolizumab Biosimilar RPH-075; RPH 075; RPH-075; RPH075; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Echocardiography; Undergo echocardiography; Other Names: EC; Biological: Autologous Tumor Membrane Vesicles Vaccine; Given intradermally; Other Names: Autologous TDMV-derived Vaccine; Autologous TMV Vaccine; Autologous TMV-based Vaccine; Autologous Tumor-derived Membrane Vesicles Vaccine; Procedure: Surgical Procedure; Provide tissue from standard of care surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of treatment up to 7 weeks
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.	Up to 30 days after last dose of treatment
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.	Up to 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Before and after each vaccination up to 6 weeks
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.	Up to 12 months
Progression-free survival (PFS)	PFS rates will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test.	From start of treatment to time of progression or death up to 12 months
Overall survival (OS)	OS rates will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test.	From start of treatment to time of death up to 12 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Dong M. Shin, MD, FACP, FAAAS, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 5, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Recurrent or metastatic head and neck cancer whose tumor should have banked at the time of surgery.
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Carcinoma, Squamous Cell; Laryngeal Diseases; Nasopharyngeal Neoplasms; Pathological Conditions, Signs and Symptoms; Nasopharyngeal Carcinoma; Squamous Cell Carcinoma of Head and Neck; Recurrence; Carcinoma; Laryngeal Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Spectrum Analysis; Specimen Handling; pembrolizumab; Magnetic Resonance Spectroscopy; Surgical Procedures, Operative
• Other Study ID Numbers: STUDY00006705 (Other Identifier: Emory University Hospital/Winship Cancer Institute); P30CA138292 (U.S. NIH Grant/Contract); NCI-2024-08422 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Winship6045-23 (Other Identifier: Emory University Hospital/Winship Cancer Institute); 1R01CA262123-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No