Immunotherapy + Radiation for Head and Neck Cancer

Overseen By Jonathan D. Schoenfeld, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antiretrovirals, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disease, HIV, 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

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

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combined approach of immunotherapy (using pembrolizumab, also known as KEYTRUDA) and radiation therapy to treat head and neck cancer that has worsened or spread. The researchers aim to determine if this combination can better control the cancer compared to previous treatments. Suitable participants have head and neck cancer that hasn't responded to other treatments and have experienced disease progression after previous PD-1 therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other cancer-specific therapy while participating. You must also be at least 2 weeks from your last chemotherapy, biological agents, immunotherapy, or investigational drug, with adequate recovery from any side effects.

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

Research has shown that pembrolizumab, the immunotherapy used in this study, is generally well-tolerated by patients. Real-world data indicate that serious side effects are rare, with most individuals experiencing only mild to moderate side effects, such as tiredness or skin reactions. Recent studies have not identified any new safety concerns.

For the radiation therapy component, research shows it is a safe and common treatment for head and neck cancer. Advanced methods like intensity-modulated radiation therapy (IMRT) have demonstrated good safety results, reducing side effects without compromising treatment effectiveness.

Overall, both treatments in this study have a strong safety record. Serious issues are uncommon, and most side effects can be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immunotherapy with radiation to tackle head and neck cancer in a novel way. While standard treatments like surgery, chemotherapy, and radiation therapy target the cancer directly, pembrolizumab works by activating the immune system to recognize and fight cancer cells. What sets these investigational treatments apart is the combination of pembrolizumab with different radiation strategies, potentially enhancing the immune response and improving outcomes. This dual approach could lead to more effective treatment with fewer side effects compared to traditional methods.

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

Research has shown that pembrolizumab, also known as KEYTRUDA, can effectively treat head and neck cancer. It has been proven to help patients with cancer that has returned or spread live longer. For those whose cancer has worsened or spread, pembrolizumab may significantly extend survival compared to standard treatments. In this trial, some participants will receive a combination of pembrolizumab with high-dose radiation, while others will receive pembrolizumab with both high and low-dose radiation. Radiation therapy, which targets and shrinks tumors, could enhance the effectiveness of pembrolizumab. Improved radiation therapy focuses on destroying tumors while protecting healthy tissue. Together, these treatments offer a promising approach for difficult cases of head and neck cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Jonathan D. Schoenfeld, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with confirmed metastatic squamous cell carcinoma of the head and neck, who have not benefited from previous PD-1 therapy, can join. They must be in good health otherwise, with proper organ function and no serious heart issues or infections like hepatitis. Pregnant women and those with certain other cancers or autoimmune diseases cannot participate.

Inclusion Criteria

My cancer is a type that started in my head or neck and has spread, with no cure from surgery or radiation.

I am fully active or can carry out light work.

My cancer progressed or didn't improve after treatment with a PD-1 inhibitor.

Exclusion Criteria

Participants who are receiving any other investigational agents

Pregnant women

Individuals with a history of a different malignancy except under specific circumstances

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose radiation in 3 fractions and low dose radiation in 2 fractions, with pembrolizumab administered intravenously on day one of each cycle

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Radiation Therapy

Trial Overview The trial is testing pembrolizumab (KEYTRUDA), an immunotherapy drug, combined with radiation therapy to treat advanced head & neck cancer. The study aims to see if this combination helps patients whose cancer has spread despite prior treatments.

How Is the Trial Designed?

Group I: High Dose Radiation + Pembrolizumab Experimental Treatment 2 Interventions

* High dose radiation will be given in 3 fractions * Pembrolizumab administered intravenously on day one of each cycle.

Group II: High Dose + Low Dose Radiation + Pembrolizumab Experimental Treatment 2 Interventions

* High Dose radiation will be given in 3 fractions * Low Dose Radiation will be given in 2 fractions * Pembrolizumab administered intravenously on day one of each cycle.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

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 (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 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]

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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]

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]

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. 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.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02508

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

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-compared-to-standard-of-care-as-monotherapy-and-in-combination-with-chemotherapy-as-first-line-treatment-for-patients/

Merck's KEYTRUDA (pembrolizumab) Significantly ... “In this study, KEYTRUDA showed the potential to significantly prolong survival when used as first-line therapy for patients whose head and neck cancer had ...

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 ...