714 Participants Needed

Pembrolizumab + Radiotherapy for Head and Neck Cancer

Recruiting at 203 trial locations
TF
Overseen ByToll Free Number
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop as these are part of the exclusion criteria.

What data supports the effectiveness of the treatment Pembrolizumab + Radiotherapy for Head and Neck Cancer?

Research shows that pembrolizumab, when used with radiotherapy, has shown promise in treating head and neck cancer, with studies indicating it can be safe and feasible. Pembrolizumab has also demonstrated antitumor activity in head and neck cancers, especially in tumors with high PD-L1 levels, suggesting it could be effective in combination with other treatments like radiotherapy.12345

Is the combination of pembrolizumab and radiotherapy safe for treating head and neck cancer?

Pembrolizumab, when used for head and neck cancer, has been found to be generally safe, but it can cause serious side effects like pneumonia (lung infection), breathing difficulties, confusion, vomiting, and immune system-related issues such as inflammation of the lungs, liver, and intestines. Combining it with radiotherapy has been shown to be safe and feasible in early studies.12678

How is the drug pembrolizumab combined with radiotherapy unique for treating head and neck cancer?

Pembrolizumab, an immune checkpoint inhibitor, is unique because it enhances the body's immune response against cancer cells and is used in combination with radiotherapy to potentially improve outcomes for patients with locally advanced head and neck cancer, especially those who cannot tolerate standard chemotherapy like cisplatin.126910

What is the purpose of this trial?

This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes will be stratified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves event-free survival compared to radiotherapy (with or without cisplatin) given after surgery alone.

Research Team

MD

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with newly diagnosed, resectable Stage III/IVA head and neck squamous cell carcinoma. Participants must not be pregnant or breastfeeding, agree to use contraception, have no prior anti-PD-1/L1/L2 therapy or cancer treatment, no live vaccines in the last 30 days, and no immunosuppressive conditions.

Inclusion Criteria

My oropharyngeal cancer has been tested for HPV status.
I agree to use birth control during and up to 6 months after the study.
My doctor agrees I can have the main surgery for my condition.
See 6 more

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.
I am highly allergic to pembrolizumab, radiotherapy, cisplatin, or similar treatments.
I have severe bleeding caused by my cancer.
See 20 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 200 mg pembrolizumab by IV infusion on Day 1 of a 21-day cycle for 2 cycles prior to surgery

6 weeks
2 visits (in-person)

Surgery

Participants undergo surgical resection of the tumor

1 week
1 visit (in-person)

Adjuvant Treatment

High risk participants receive pembrolizumab, radiotherapy, and cisplatin; low risk participants receive pembrolizumab and radiotherapy

45 weeks
15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 92 months

Treatment Details

Interventions

  • Cisplatin
  • Pembrolizumab
  • Radiotherapy
Trial Overview The study tests pembrolizumab given before surgery and combined with post-surgery radiotherapy (with or without cisplatin) against standard care. It aims to see if this improves event-free survival in patients whose tumors express a protein called PD-L1.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Pembro Neoadjuvant+Pembro SOC AdjuvantExperimental Treatment5 Interventions
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Group II: No Neoadjuvant+SOC AdjuvantActive Control4 Interventions
Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials
2,287
Recruited
4,582,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

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 profile image

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

Findings from Research

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.
However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.Tao, Y., Biau, J., Sun, XS., et al.[2023]
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.
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 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.
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]

References

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]
Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]
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]
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. [2019]
Pembro Ups Survival in PD-L1-positive HNSCC. [2019]
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. [2019]
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]
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]
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]
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