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)
5 other identifiers
interventional
40
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2025
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2025
CompletedFirst Posted
Study publicly available on registry
March 11, 2025
CompletedStudy Start
First participant enrolled
May 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
March 4, 2026
March 1, 2026
2.7 years
March 5, 2025
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (4)
Vaccine-induced immune response
Before and after each vaccination up to 6 weeks
Tumor response rate
Up to 12 months
Progression-free survival (PFS)
From start of treatment to time of progression or death up to 12 months
Overall survival (OS)
From start of treatment to time of death up to 12 months
Study Arms (2)
Cohort 1 (TMV vaccine therapy)
EXPERIMENTALPatients 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.
Cohort 2 (TMV vaccine therapy, pembrolizumab)
EXPERIMENTALPatients 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.
Interventions
Given intradermally
Undergo blood sample collection
Undergo CT
Undergo echocardiography
Undergo MRI
Given IV
Undergo PET
Provide tissue from standard of care surgery
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Emory Universitylead
- National Cancer Institute (NCI)collaborator
- National Institutes of Health (NIH)collaborator
Study Sites (2)
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dong M. Shin, MD, FACP, FAAAS
Emory University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 5, 2025
First Posted
March 11, 2025
Study Start
May 8, 2025
Primary Completion (Estimated)
January 31, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
March 4, 2026
Record last verified: 2026-03