Cisplatin + Pembrolizumab for Head and Neck Cancer

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trisha Wise-Draper

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Metastatic disease, HPV+, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding pembrolizumab, a drug that helps the immune system fight cancer, to the usual treatments for head and neck cancer can improve outcomes. Usual treatments include surgery and six weeks of radiation, with some patients also receiving the chemotherapy drug cisplatin if their cancer is considered "high risk." Suitable candidates for this trial have head and neck cancer requiring surgery and may have large tumors or cancer spread to lymph nodes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

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

Previous studies have shown that pembrolizumab is generally well-tolerated by patients with head and neck cancer. Although serious side effects have been recorded, they are rare and usually manageable. Most people experience mild to moderate side effects. Additionally, no new safety concerns have emerged when pembrolizumab is used before and after surgery.

Cisplatin, another treatment in this study, is a standard chemotherapy drug used for many years. While effective, it can cause side effects like nausea or tiredness. However, these side effects are well-known and usually treatable.

Overall, the treatments in this study have been used before and have a known safety record. For concerns, discussing them with the study team might help in understanding how they handle any potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard treatments for head and neck cancer, which typically involve a combination of surgery, radiation, and chemotherapy like cisplatin, pembrolizumab offers a novel approach. Pembrolizumab is an immunotherapy drug that works by blocking a protein called PD-1, helping the immune system recognize and attack cancer cells more effectively. Researchers are excited about pembrolizumab because it has the potential to enhance the body's natural defenses against cancer, potentially improving outcomes and reducing the reliance on more toxic treatments like chemotherapy. This innovative mechanism of action sets it apart from traditional therapies and offers hope for more effective and targeted cancer treatment.

What evidence suggests that adding pembrolizumab to standard treatment could be effective for head and neck cancer?

Research shows that pembrolizumab may help treat head and neck cancer. In this trial, participants will receive pembrolizumab combined with standard surgery, followed by radiation therapy, with or without cisplatin. Studies have found that adding pembrolizumab to standard care helped patients with locally advanced cases live longer without cancer progression. Another study found that using pembrolizumab with chemotherapy improved overall survival rates for some patients. Cisplatin, a well-known treatment, is often used with radiation therapy, and both weekly and triweekly doses have shown similar survival results for head and neck cancer patients. Overall, evidence supports that combining pembrolizumab with standard treatments like cisplatin and radiation therapy could effectively fight head and neck cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Trisha Wise-Draper, MD,PhD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for adults with head and neck squamous cell carcinoma who are fit enough for surgery, have certain high-risk cancer features, and can handle standard treatments. They must not have immune deficiencies, be on recent immunosuppressants, or have specific other cancers or infections like TB or hepatitis.

Inclusion Criteria

I am willing to have surgery to remove a tumor and neck lymph nodes.

I can carry out all my usual activities without help.

Adequate labs

Exclusion Criteria

My throat cancer is caused by HPV.

My cancer is located in the nasopharynx or sinonasal region.

I have an immune system disorder or have been on steroids or immune-suppressing drugs within the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo surgery as part of the standard of care treatment

1 week

1 visit (in-person)

Radiation

Participants receive radiation therapy for 6 weeks

6 weeks

6 visits (in-person, weekly)

Chemotherapy

High-risk participants receive cisplatin once a week for 6 weeks

6 weeks

6 visits (in-person, weekly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Pembrolizumab
• Radiation Therapy
• Surgery

Trial Overview The study tests adding pembrolizumab to the usual care (surgery plus radiation) for head and neck cancer. Some patients may also get cisplatin if their cancer is 'high risk'. The goal is to see if pembrolizumab improves outcomes when combined with these standard therapies.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 4 Interventions

Pembrolizumab in combination with standard of care surgery followed by radiation therapy with or without cisplatin

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Trisha Wise-Draper

Lead Sponsor

Trials

6

Recruited

230+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

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 comparing cisplatin and cetuximab added to radiation therapy for head and neck squamous cell carcinoma, patients receiving cisplatin had a significantly higher 3-year disease-specific survival rate of 83% compared to 31% for those receiving cetuximab.

Cisplatin treatment was associated with a lower recurrence rate of disease (4 patients) compared to cetuximab (17 patients), indicating that cisplatin may be more effective in improving outcomes when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Ley, J., Mehan, P., Wildes, TM., et al.[2021]

In a study of 1,149 patients with advanced head and neck squamous cell carcinoma, carboplatin-based chemoradiotherapy showed similar cancer-specific mortality rates compared to cisplatin-based therapy, indicating that carboplatin can be an effective alternative for patients unable to receive cisplatin.

Both carboplatin and cisplatin-based chemoradiotherapy were found to be more effective than radiation therapy alone or radiation with cetuximab, suggesting that carboplatin should be further investigated as a viable treatment option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Xiang, M., Colevas, AD., Holsinger, FC., et al.[2020]

Pemetrexed shows promising efficacy as a treatment for head and neck cancer, particularly when used in combination with other chemotherapeutic agents or radiotherapy, based on a review of ten studies.

The drug has an acceptable safety profile, with fewer severe nonhematologic toxicities compared to cisplatin, making it a potential alternative worth further investigation, especially as a radiosensitizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in head and neck cancer: a systematic review. Argiris, A., Pennella, E., Koustenis, A., et al.[2018]

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 4520 patients with stage III to IVb head and neck squamous cell carcinoma, those treated with cisplatin alongside radiation therapy had significantly better overall survival compared to those treated with cetuximab, with a median survival of 4.1 years versus 1.7 years for cetuximab.

After adjusting for treatment biases, cetuximab continued to show inferior overall survival rates, suggesting that cisplatin is a more effective partner for radiation therapy in the nonoperative management of this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. Bauml, JM., Vinnakota, R., Anna Park, YH., et al.[2023]

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]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

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 of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Citations

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Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... The National Comprehensive Cancer Network guideline recommends high-dose cisplatin delivered every 3 weeks as a category 1, preferred concurrent ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772906025000263

Review Article Comparing efficacy and safety of weekly vs. ... Both weekly and triweekly cisplatin regimens show comparable survival outcomes and safety profiles in patients with head and neck cancers, except for short term ...

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Disease outcome and associated factors after definitive ... A failure-type specific risk prediction tool for selection of head-and-neck cancer patients for experimental treatments

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01293

Weekly Cisplatin Plus Radiation for Postoperative Head ... Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9875652/

Treatment outcomes of standard (high dose) cisplatin and non ... Weekly LD‐cisplatin resulted in a similar efficacy with a better safety profile, but the non‐cisplatin regimens had relatively poor clinical ...

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

Real-World Evidence on the Effectiveness of Pembrolizumab ... Safety and efficacy outcomes in head and neck cancer (HNC) patients (pts) treated with first-line (1l) pembrolizumab (p), alone or with ...

7. 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, ...

8. 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 ...

9. 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 ...

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

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp ...