TMV Vaccine + Pembrolizumab for Head and Neck Cancer

Recruiting at 1 trial location

Overseen By Dong M. Shin, MD, FACP, FAAAS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Active infection, others

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

Compensation: Varies

Number of Visits: 92

Duration: Up to 1 year

12 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressants or systemic corticosteroids, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Pembrolizumab for head and neck cancer?

Pembrolizumab has shown antitumor activity in patients with recurrent or metastatic head and neck squamous cell carcinoma, especially in those with PD-L1-positive tumors, and is approved as a first-line treatment in these cases. It has been studied in combination with chemoradiation for locally advanced cases, demonstrating safety and feasibility. ^{1 2 3 4 5}

Is the TMV Vaccine + Pembrolizumab treatment safe for humans?

Pembrolizumab, used in treating head and neck cancer, has a safety profile similar to other PD-1 inhibitors, with common side effects like diarrhea, skin rash, and thyroid issues, and rare serious lung inflammation. Some patients may experience faster tumor growth, and immune-related skin and mouth issues can occur, requiring careful management. ^{1 2 6 7 8}

How is the TMV Vaccine + Pembrolizumab treatment different for head and neck cancer?

The TMV Vaccine + Pembrolizumab treatment is unique because it combines a vaccine therapy with pembrolizumab, an immune checkpoint inhibitor, potentially enhancing the immune system's ability to fight head and neck cancer. This combination may offer a novel approach compared to standard treatments, which often involve chemoradiation or surgery. ^{1 3 9 10 11}

What is the purpose of 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.

Research Team

Dong M. Shin, MD, FACP, FAAAS

Principal Investigator

Emory University

Eligibility Criteria

This trial is for patients with recurrent or metastatic head and neck squamous cell cancer. Participants should have a type of skin, throat, nasal, oral, or laryngeal cancer that has returned after treatment or spread to other body parts.

Inclusion Criteria

Various hematologic and biochemical parameters within specified ranges

Ability to understand and willingness to sign written informed consent documents

Tumors should be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

Exclusion Criteria

My cancer is a non-squamous cell type in the head or neck, or is a salivary gland tumor.

My surgery did not collect enough tissue for 3 doses.

I am on long-term immunosuppressants or have had an organ or bone marrow transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Cohort 2 also receives pembrolizumab IV on day 1 of each cycle, with cycles repeating every 3 weeks for up to 1 year.

Up to 1 year

Every 2 weeks for TMV vaccine, every 3 weeks for pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up on day 90 and every 3 weeks for up to 12 months.

12 months

Follow-up on day 90, then every 3 weeks

Treatment Details

Interventions

• Pembrolizumab
• TMV Vaccine Therapy

Trial Overview The trial is testing the safety and optimal dose of TMV vaccine therapy alone and combined with pembrolizumab. It aims to see how well these treatments help the immune system fight off cancer in patients with advanced head and neck cancers.

Participant Groups

Group I: Cohort 2 (TMV vaccine therapy, pembrolizumab) Experimental Treatment 8 Interventions

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 II: Cohort 1 (TMV vaccine therapy) Experimental Treatment 7 Interventions

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.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, where tumor growth accelerated during treatment.

Hyperprogression was significantly associated with regional recurrence, leading to shorter progression-free survival, but did not affect overall survival, highlighting the need for further research into the mechanisms behind this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Saâda-Bouzid, E., Defaucheux, C., Karabajakian, A., et al.[2022]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a study of 646 adults with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), real-world outcomes showed that pembrolizumab, whether used alone or with chemotherapy, provided similar overall survival rates to those seen in clinical trials, with median overall survival of 12.1 months for monotherapy and 11.9 months for combination therapy.

Factors such as HPV-positive tumor status and lower Eastern Cooperative Oncology Group performance status were associated with longer overall survival, highlighting the importance of tumor characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma. Black, CM., Hanna, GJ., Wang, L., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a study of 36 patients with resectable HPV-unrelated head and neck squamous-cell carcinoma, neoadjuvant pembrolizumab was found to be safe, with no serious adverse events reported during treatment.

The treatment resulted in a pathologic tumor response in 44% of patients, and the one-year relapse rate for those with high-risk pathology was significantly lower at 16.7%, compared to the historical rate of 35%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Uppaluri, R., Campbell, KM., Egloff, AM., et al.[2021]

Pembrolizumab has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a phase Ib/III trial involving 36 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab showed a tolerable safety profile, with only one reported dose-limiting toxicity (fatal arterial hemorrhage) and no other treatment-related fatalities.

The combination therapy resulted in a confirmed partial response in 13.9% of patients, with median progression-free survival of 3.0 months and overall survival of 5.8 months, indicating that its efficacy was comparable to pembrolizumab alone based on historical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Harrington, KJ., Kong, A., Mach, N., et al.[2021]

References

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

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. [2022]

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

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. [2022]

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

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

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

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. [2021]

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

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. [2021]

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

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]

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

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. [2023]

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

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. [2021]