Pembrolizumab for Head and Neck Cancers

Not currently recruiting at 3 trial locations

Overseen By Ryan Brisson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 17

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug pembrolizumab (also known as KEYTRUDA or MK-3475) can help prevent the return of head and neck cancer. It compares pembrolizumab to a placebo (a substance with no therapeutic effect) to assess whether it extends the time patients remain free from cancer progression. Individuals who have completed their main cancer treatment but still face a high risk of recurrence may be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

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

Research has shown that pembrolizumab is generally well-tolerated. Studies have found that while it can cause some side effects, these are often manageable. In real-world use, pembrolizumab has been safely administered to patients with certain types of head and neck cancer, demonstrating positive effects in those with recurring or hard-to-treat forms of the disease.

Pembrolizumab is already FDA-approved for other conditions, indicating a reasonable level of safety. However, like any treatment, it may cause side effects such as tiredness, skin rash, or changes in blood tests. Serious side effects are less common but can occur.

Safety data from previous studies also show that pembrolizumab, when combined with other treatments, remains effective and safe for many patients. Participants in those studies experienced improved survival without a significant increase in severe side effects.

Overall, while pembrolizumab is considered safe for many, discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

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

Pembrolizumab is unique because it leverages the power of immunotherapy to target head and neck cancers. Unlike standard treatments like chemotherapy and radiation, which directly attack cancer cells, pembrolizumab works by unleashing the body’s immune system to recognize and fight cancer cells more effectively. This is achieved through its action as a PD-1 inhibitor, blocking a pathway that cancer cells use to hide from the immune system. Researchers are excited about pembrolizumab because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes compared to traditional therapies.

What evidence suggests that pembrolizumab might be an effective treatment for head and neck cancers?

Research has shown that pembrolizumab effectively treats head and neck squamous cell carcinoma, particularly when the cancer has returned or spread. The KEYNOTE-048 study demonstrated that using pembrolizumab alone or with chemotherapy improved survival rates for these patients. In this trial, participants will receive either pembrolizumab or a placebo. For those with serious cancer that hasn't spread, adding pembrolizumab before and after surgery reduced issues like cancer recurrence. The FDA has approved this treatment for such situations, confirming its effectiveness and safety. These findings suggest pembrolizumab could benefit individuals at high risk of cancer recurrence. ^{6 7 8 9 10}

Who Is on the Research Team?

Alexander Pearson, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults with head and neck squamous cell carcinoma who've finished curative treatment within the last 20 weeks, at high risk of cancer coming back. They must have good performance status, agree to use contraception, and not be pregnant or breastfeeding. Excluded are those with active infections like TB or hepatitis, recent other treatments or trials, certain autoimmune diseases, another progressing cancer, CNS metastases, or a history of severe reactions to pembrolizumab.

Inclusion Criteria

I can provide at least 10 slides of my tumor for testing.

Be willing and able to provide written informed consent/assent for the trial

I agree to use birth control during and for 4 months after the study.

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.

I have a history of HIV or active Hepatitis B/C.

Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of trial treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant pembrolizumab or placebo every three weeks for one year

52 weeks

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Placebo

Trial Overview The PATHWay Study is testing if pembrolizumab can prevent cancer from returning in patients with high-risk head and neck cancers after they've completed their main treatment. Participants will either receive pembrolizumab or a placebo for one year in this double-blind study where neither doctors nor patients know who's getting the real drug.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

iv, every 3 weeks, x 1 year

Group II: Pembrolizumab Experimental Treatment 1 Intervention

200mg, every three weeks, iv, x 1 year

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

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]

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 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 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]

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 study of 257 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab, biomarkers such as tumor mutational burden (TMB), PD-L1 expression, and T-cell-inflamed gene expression profile (Tcellinf GEP) were found to be significantly associated with overall response rates (ORR) to the treatment.

The study indicated that higher levels of these biomarkers correlated with better treatment responses, suggesting that they could be useful in predicting how well patients will respond to pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers predictive of response to pembrolizumab in head and neck cancer. Pfister, DG., Haddad, RI., Worden, FP., et al.[2023]

Citations

1. 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.

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. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-and-adjuvant-pembrolizumab-resectable-locally-advanced-head-and-neck

FDA approves neoadjuvant and adjuvant pembrolizumab ... FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma · Efficacy and Safety.

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. 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. Official Title. A Phase III ...

6. 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.

7. dana-farber.org dana-farber.org/newsroom/news-releases/2025/immunotherapy-before-and-after-surgery-improves-outcomes-in-head-and-neck-cancer

Immunotherapy before and after surgery improves ... This trial, called KEYNOTE-689, is the first study in more than 20 years to show improvements in outcomes over standard of care for this patient ...

8. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02358031

NCT02358031 | A Study of Pembrolizumab (MK-3475) for ... Per protocol, response/progression or adverse events (AEs) that occur during the second pembrolizumab course will not be counted towards efficacy outcome ...