Pembrolizumab + Anti-platelet Therapy for Head and Neck Cancer

Overseen By Christina Godwin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical University of South Carolina

Must be taking: Anti-platelet therapy

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, NSAIDs

Disqualifiers: Bleeding disorder, Autoimmune disease, Cardiovascular disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining anti-platelet therapy with pembrolizumab (an immunotherapy) can enhance the immune response in individuals with recurrent or metastatic head and neck cancer. Participants will receive either pembrolizumab with anti-platelet drugs like aspirin and clopidogrel or pembrolizumab alone, in different sequences. The trial targets individuals whose cancer has returned or spread, especially those who have already undergone treatments like chemotherapy. If a doctor has confirmed that your cancer fits these criteria and it affects your daily life, this trial might suit you. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this potentially groundbreaking therapy.

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

The trial requires a 7-day washout period (time without taking certain medications) for those on anticoagulation or NSAID therapy. If you are on immunosuppressive therapy, chemotherapy, immunotherapy, or monoclonal antibodies, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, a drug used in immunotherapy, has been tested in many studies. These studies found that pembrolizumab alone did not cause any new safety issues, indicating it was generally safe for patients.

Researchers are now exploring whether combining pembrolizumab with aspirin and clopidogrel (both drugs that help prevent blood clots) can enhance treatment for head and neck cancer. However, detailed safety information about this combination is not yet available. Since this study is in its early stages, the primary goal is to gather safety information.

Pembrolizumab is already FDA-approved for other conditions, meaning its safety is well-known for those uses. However, when combined with other drugs like aspirin and clopidogrel, it is crucial to observe how patients react to the mix. Participants in the trial will help researchers learn more about any side effects or risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for head and neck cancer because it combines pembrolizumab, a type of immunotherapy, with anti-platelet therapy, which includes ASA (aspirin) and clopidogrel. Unlike standard treatments that often focus solely on targeting cancer cells, this approach aims to enhance the immune response against cancer while potentially improving blood flow and reducing clot-related complications. By targeting both the immune system and blood platelets, this combination could offer a more comprehensive attack on the cancer, potentially leading to better outcomes. This dual-action strategy is what sets it apart from more conventional treatments like surgery, radiation, and chemotherapy.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that pembrolizumab effectively treats head and neck squamous cell carcinoma (HNSCC). Studies have found that using pembrolizumab alone or with chemotherapy can extend the lives of patients with recurring or spreading HNSCC. Pembrolizumab is particularly effective in patients with high levels of a protein called PD-L1, which aids the immune system in fighting cancer cells. In this trial, participants in Group 1 will receive pembrolizumab combined with anti-platelet drugs like ASA and clopidogrel, followed by pembrolizumab alone. Participants in Group 2 will start with pembrolizumab alone, followed by the combination with ASA and clopidogrel. Although the combination of pembrolizumab with anti-platelet drugs is still under study, its success in treating similar conditions suggests potential effectiveness. ^{1 4 6 7 8}

Who Is on the Research Team?

John Kaczmar, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that expresses PD-L1 or has progressed after chemotherapy can join. They must have a life expectancy of at least 3 months, measurable disease, good performance status, and adequate organ function. Women who can bear children need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

My kidneys work well enough, with a creatinine clearance over 30 mL/min.

Subject has adequate hematologic function: ANC >1000 K/CUMM, Hemoglobin >8.0 Grams/dL, Platelets >75,000 K/CUMM, INR < 1.7

My cancer can be measured and has grown in areas previously treated with radiation.

Exclusion Criteria

I do not have any major health issues that could affect my treatment.

I have not received any vaccines within 4 weeks before starting pembrolizumab, except for inactivated ones.

I am on blood thinners but can stop them for 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Regimen A

Participants receive pembrolizumab, ASA, and clopidogrel daily for 6 weeks

6 weeks

Treatment Regimen B

Participants receive pembrolizumab alone for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetylsalicylic acid
• Clopidogrel
• Pembrolizumab

Trial Overview The trial is testing if combining Pembrolizumab (an immunotherapy drug) with anti-platelet drugs like acetylsalicylic acid and Clopidogrel improves immune response in patients compared to just using immunotherapy alone.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 3 Interventions

Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.

Group II: Group 1 Experimental Treatment 3 Interventions

Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

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 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]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

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]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804925001765

5-year follow-up from the randomized phase III KEYNOTE- ... Previous results of the phase 3 KEYNOTE-048 study showed that pembrolizumab significantly improved overall survival (OS) compared with cetuximab ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042?tab=results

Study Results | Pembrolizumab (MK-3475) Versus ... Serious AEs and Other AEs were reported according to treatment course for all randomized participants who received ≥1 dose of study treatment. Per protocol, ...

7. merck.com merck.com/news/keytruda-pembrolizumab-as-perioperative-treatment-with-standard-of-care-soc-adjuvant-therapy-significantly-improved-event-free-survival-compared-to-soc-alone-in-patients-with-resectable-loca/

KEYTRUDA® (pembrolizumab) as Perioperative Treatment ... Results at the first interim analysis of the trial showed KEYTRUDA significantly improved event-free survival (EFS) as part of a perioperative treatment regimen ...

8. clinicaltrialsarena.com clinicaltrialsarena.com/news/msd-keytruda-combo/

MSD reports outcomes from trial of Keytruda combination ... After a median follow-up at 38.3 months, the therapy had decreased the EFS event risk by 34% in subjects whose combined positive score (CPS) was ...