Petosemtamab + Pembrolizumab for Head and Neck Cancer

Recruiting at 194 trial locations

Overseen By Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merus N.V.

Must be taking: Pembrolizumab

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Cardiac issues, others

No Placebo Group All 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 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: Unknown

Duration: Until disease progression or unacceptable toxicity

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new combination of two treatments, petosemtamab and pembrolizumab (also known as KEYTRUDA), for individuals with a type of head and neck cancer that has recurred or spread and shows a specific protein (PD-L1). The goal is to determine if the combination is more effective than pembrolizumab alone in treating this cancer. It suits those with this type of cancer in areas like the throat or mouth who have not yet received drug treatment for its current state. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had any systemic anticancer therapy within 4 weeks before starting the study treatment.

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

Earlier studies have shown that the combination of petosemtamab and pembrolizumab holds promise for treating head and neck cancer. Research suggests that patients generally tolerate this combination well. Specifically, 63% of 43 patients responded positively, with their cancer either shrinking or stopping growth. Additionally, 79% of patients remained alive after one year.

Pembrolizumab alone has already received approval for some cancer types, so its safety profile is well-established. It may cause tiredness, rash, or diarrhea, but these side effects are usually manageable.

Joining a trial can provide access to new treatments, but understanding the potential risks is crucial. Always consult a healthcare professional to determine if it is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for head and neck cancer?

Researchers are excited about the combination of Petosemtamab and Pembrolizumab for head and neck cancer because it offers a unique dual approach. While Pembrolizumab is already known for boosting the immune system to attack cancer cells, Petosemtamab introduces a new mechanism by targeting specific cancer cell receptors, potentially making the treatment more effective. This combination could enhance the body's immune response more than current standard treatments like chemotherapy or radiation. Additionally, the possibility of improved efficacy with fewer side effects is a promising advancement for patients dealing with this challenging condition.

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

Research has shown that combining petosemtamab with pembrolizumab, which participants in this trial may receive, may effectively treat recurring or spreading head and neck cancer. In one study, 63% of patients responded to the combination treatment, and 79% were still alive after one year. On average, patients lived nine months without their cancer worsening. Petosemtamab targets specific proteins on cancer cells, enhancing pembrolizumab's effectiveness. This combination treatment could offer new hope for patients with limited options. Another group in this trial will receive pembrolizumab alone as monotherapy. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with a type of cancer called PD-L1+ recurrent or metastatic head and neck squamous cell carcinoma. Participants must be receiving their first round of treatment for this condition.

Inclusion Criteria

Measurable disease as defined by RECIST v1.1 by radiologic methods

Signed ICF before initiation of any study procedures

Life expectancy ≥ 12 weeks, as per investigator assessment

Exclusion Criteria

My brain metastases are either untreated, still causing symptoms, or need more treatment.

My cancer has spread to the lining of my brain and spinal cord.

I haven't had cancer treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive petosemtamab plus pembrolizumab or pembrolizumab alone as first-line treatment for recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days post-last dose

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Petosemtamab

Trial Overview The study compares two treatments: one group receives Petosemtamab plus Pembrolizumab, while the other gets only Pembrolizumab. It's designed to see which combination is more effective as a first-line treatment.

How Is the Trial Designed?

Group I: Petosemtamab + Pembrolizumab Experimental Treatment 2 Interventions

Combination Therapy

Group II: Pembrolizumab Active Control 1 Intervention

Monotherapy

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?

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Published Research Related to This Trial

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 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]

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 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 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]

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 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]

A 69-year-old patient with relapsed squamous cell carcinoma showed significant improvement after 14 cycles of pembrolizumab, indicating its efficacy as a second-line treatment for metastatic head and neck cancer.

The patient developed severe immune-related adverse effects, specifically grade 4 mucositis and esophagitis, highlighting the importance of monitoring for such complications in patients receiving PD-1 inhibitors like pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. Acero Brand, FZ., Suter, N., Adam, JP., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6024

Petosemtamab (MCLA-158) with pembrolizumab as first- ... Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab continues to demonstrate promising clinical efficacy and a ...

2. ir.merus.nl ir.merus.nl/news-releases/news-release-details/merus-petosemtamab-pembrolizumab-interim-data-demonstrates

Merus' Petosemtamab with Pembrolizumab Interim Data ... 63% response rate observed among 43 evaluable patients. - 79% overall survival rate at 12-months; 9 months median progression-free survival.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40511820/

LiGeR-HN phase III trials of petosemtamab ... Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06525220

NCT06525220 | A Phase 3 Study to Evaluate ... This is a Phase 3 randomized, open-label study to evaluate the efficacy and safety of petosemtamab plus pembrolizumab vs pembrolizumab in first-line treatment

5. targetedonc.com targetedonc.com/view/petosemtamab-and-pembrolizumab-a-promising-pair-in-hnscc-treatment

Petosemtamab & Pembrolizumab: Promising HNSCC Treatment A phase 2 study evaluating petosemtamab plus pembrolizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

6. onclive.com onclive.com/view/petosemtamab-mcla-158-with-pembrolizumab-as-first-line-1l-treatment-of-pd-l1-recurrent-metastatic-r-m-head-and-neck-squamous-cell-carcinoma-hnscc-phase-2-trial-

Petosemtamab (MCLA-158) With Pembrolizumab as First ... Carla van Herpen, MD, PhD, presents phase 2 trial results showing that petosemtamab plus pembrolizumab in first-line PD-L1–positive recurrent/ ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12218485/

LiGeR-HN phase III trials of petosemtamab + pembrolizumab ... Global treatment patterns and outcomes among patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results of the GLANCE H&N study.