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Interventional Trials in Metastatic Head and Neck SCC (CT, public)

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July 29, 2025

phase 3 metastatic squamous cell carcinoma of head and neck that started after 2015 that are also interventional and industry sponsored

Twenty-one phase 3, interventional, industry-sponsored trials in metastatic head and neck squamous cell carcinoma have been initiated since 2015, with varying current status ranging from recruiting to terminated.

Abstract

Twenty-one phase 3, interventional, industry‐sponsored trials in metastatic head and neck squamous cell carcinoma initiated after 2015 have been registered. Fifteen trials evaluate anti–PD-1/PD-L1 agents as single agents or in combination, while 12 assess these agents paired with novel immunotherapies (for example, bispecific antibodies, vaccines, fusion proteins) or with tyrosine kinase inhibitors, chemotherapy, or anti–EGFR therapy.

Seventeen studies list overall survival, progression-free survival, and response rate as primary endpoints but have not reported results. No study has detailed quantitative safety outcomes such as grade 3–4 adverse events or treatment discontinuations. Enrollment is often limited by biomarker criteria (eg, PD-L1 Combined Positive Score thresholds or HPV16 positivity), although subgroup data are not available. Among the trials, nine are recruiting, one is active but not recruiting, two are active with published results, five have completed with available results, and three were terminated with results reported.

Methods

We analyzed 38 sources from an initial pool of 500, using 7 screening criteria. Each paper was reviewed for 5 key aspects that mattered most to the research question. More on methods

Papers identified with Elicit search

n = 500

Papers screened using: Population - Cancer Type, Population - Disease Stage, Study Design - Trial Phase, Study Design - Type, Study Sponsorship, Study Timeline, Population Exclusions

n = 500

Papers screened out

n = 462

Papers included for extraction

n = 38

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Paper search

Using your research question “phase 3 metastatic squamous cell carcinoma of head and neck that started after 2015 that are also interventional and industry sponsored”, we searched across all trials from the ClinicalTrials.gov corpus. We retrieved the 500 trials most relevant to the query.

Screening

We screened in sources based on their abstracts that met these criteria:

• Population - Cancer Type: Does the study specifically focus on patients with squamous cell carcinoma of head and neck (HNSCC)?
• Population - Disease Stage: Does the study include patients with metastatic disease?
• Study Design - Trial Phase: Is this a Phase 3 clinical trial?
• Study Design - Type: Is this an interventional study?
• Study Sponsorship: Is the study sponsored (fully or partially) by industry?
• Study Timeline: Did the study start on or after January 1, 2015?
• Population Exclusions: Does the study focus exclusively on HNSCC patients (without including other cancer types)?

We considered all screening questions together and made a holistic judgement about whether to screen in each paper.

Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

• Study Type and Phase:

Extract the specific study type (e.g., interventional) and exact phase (e.g., Phase 3) as listed in the clinical trial registration or methods section. If multiple phases are mentioned (e.g., Phase 2/3), record both.

Verification steps:

• Check clinical trial registration
• Confirm phase in methods section of full text
• If discrepancies exist, prioritize the most recent or most detailed source

Acceptable responses include:

• Interventional, Phase 3

• Interventional, Phase 2/3

• Sponsorship Details:

Identify the primary sponsor of the study. Look for:

• Industry sponsor name
• Funding source
• Sponsoring organization

Verification steps:

• Check acknowledgments section
• Review conflicts of interest statement
• Examine funding declaration

If multiple sponsors exist, list the primary industry sponsor. If no clear industry sponsor is found, note “Not specified” or “Non-industry sponsored”.

• Participant Eligibility Criteria:

Extract key inclusion and exclusion criteria specific to:

• Disease stage (metastatic squamous cell carcinoma)
• Age range
• Performance status
• Prior treatments

Specific focus areas:

• Confirm metastatic status
• Note any specific subtype restrictions
• Record minimum and maximum age
• List any critical exclusion criteria

If criteria are complex, summarize the most important points. Use direct quotes from eligibility criteria when possible.

• Geographical Locations:

List all countries where the study is being conducted.

Extraction method:

• Count total number of countries
• List each country exactly as it appears in the trial registration
• If multiple sites exist within a country, just list the country name

Example format:

• United States

• China

• Multiple European countries

• Primary Intervention:

Describe the primary intervention in detail:

• Specific drugs/treatments used
• Combination therapies
• Dosage (if specified)
• Administration method

Extraction guidelines:

• Use precise terminology from the study
• Include all components of the intervention
• Note any comparative or combination treatments

Example format: “Zanzalintinib (XL092) + Pembrolizumab” or “Cisplatin plus Raltitrexed concurrent with Radiotherapy”

Results

Characteristics of Included Studies

Study ID

Intervention Type

Primary Endpoints

Trial Status

Merck Sharp & Dohme LLC, 2025a

Pembrolizumab (neoadjuvant and adjuvant) + radiotherapy with or without cisplatin

Event-free survival

Active, not recruiting

AVEO Pharmaceuticals, Inc., 2025

Ficlatuzumab + cetuximab vs placebo + cetuximab

Efficacy (Overall Survival, Progression-Free Survival), safety

Recruiting

Merus N.V., 2025a

Petosemtamab + pembrolizumab vs pembrolizumab

Efficacy, safety

Recruiting

Merus N.V., 2025b

Petosemtamab vs investigator’s choice monotherapy

Efficacy, safety

Recruiting

GlaxoSmithKline and Merck Sharp & Dohme LLC, 2024a

GSK3359609 + pembrolizumab vs pembrolizumab

Efficacy (Overall Survival, Progression-Free Survival), safety

Terminated, results available

Inhibrx Biosciences, Inc., 2025

INBRX-106 + pembrolizumab vs pembrolizumab

Efficacy, safety

Recruiting

Akeso, 2024

AK112 + AK117 vs pembrolizumab

Efficacy, safety

Recruiting

Incyte Corporation and Merck Sharp & Dohme LLC, 2025

Pembrolizumab + epacadostat vs pembrolizumab vs EXTREME regimen (cetuximab, platinum, and 5-fluorouracil)

Efficacy, safety

Active, not recruiting, results available

Merck Sharp & Dohme LLC and Eisai Inc., 2025a

Pembrolizumab + lenvatinib vs pembrolizumab + placebo

Objective Response Rate, Progression-Free Survival, Overall Survival

Completed, results available

PDS Biotechnology Corp., 2025

PDS0101 + pembrolizumab vs pembrolizumab

Overall Survival, Objective Response Rate, Disease Control Rate, Duration of Response, Progression-Free Survival

Recruiting

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Summary of intervention types:

• Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) agents:Found in 15 studies, either alone or in combination.
• Anti-PD-1/PD-L1 agents with novel immunotherapies:12 studies tested combinations with bispecific antibodies, vaccines, fusion proteins, anti-Inducible T-cell COStimulator (ICOS), anti-NKG2A, interleukin-2 (IL-2) agonist, or indoleamine 2,3-dioxygenase (IDO) inhibitor.
• Anti-PD-1/PD-L1 agents with tyrosine kinase inhibitors:2 studies.
• Anti-PD-1/PD-L1 agents with or without chemotherapy:3 studies.
• Anti-Epidermal Growth Factor Receptor (EGFR) (cetuximab) in combination regimens:4 studies.
• Chemotherapy as comparator or Standard of Care/EXTREME regimen:4 studies.
• Cancer vaccines (PDS0101, BNT113) with anti-PD-1:2 studies.
• Novel immunotherapies (petosemtamab, SCT-I10A, AK112/AK117, INBRX-106, ficerafusp alfa) as monotherapy or in combination:6 studies.

Summary of trial status:

• 9 studies were recruiting.
• 1 study was active, not recruiting.
• 2 studies were active, not recruiting, with results available.
• 5 studies were completed, with results available.
• 3 studies were terminated, with results available.
• We didn’t find mention of the trial status for 1 study.

Summary of primary endpoints:

• 17 studies listed efficacy and safety as primary endpoints.
• 1 study listed event-free survival as the primary endpoint.
• 2 studies listed multiple efficacy endpoints (Overall Survival, Objective Response Rate, Disease Control Rate, Duration of Response, Progression-Free Survival).
• We didn’t find mention of unique primary endpoints in other studies.

Effects

Primary Outcomes

Study ID

Overall Survival

Progression-Free Survival

Response Rate

Merck Sharp & Dohme LLC, 2025a

No mention found (non-metastatic)

No mention found

No mention found

AVEO Pharmaceuticals, Inc., 2025

No mention found

No mention found

No mention found

Merus N.V., 2025a

No mention found

No mention found

No mention found

Merus N.V., 2025b

No mention found

No mention found

No mention found

GlaxoSmithKline and Merck Sharp & Dohme LLC, 2024a

No mention found (terminated)

No mention found

No mention found

Inhibrx Biosciences, Inc., 2025

No mention found

No mention found

No mention found

Akeso, 2024

No mention found

No mention found

No mention found

Incyte Corporation and Merck Sharp & Dohme LLC, 2025

No mention found

No mention found

No mention found

Merck Sharp & Dohme LLC and Eisai Inc., 2025a

No mention found

No mention found

No mention found

PDS Biotechnology Corp., 2025

No mention found

No mention found

No mention found

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Summary of findings:

• For Overall Survival:
  • 17 studies had not yet reported results.
  • 3 studies were terminated and did not report results.
  • 1 study did not report results because it was non-metastatic.
• For Progression-Free Survival:
  • 17 studies had not yet reported results.
  • 4 studies did not report results.
• For Response Rate:
  • 17 studies had not yet reported results.
  • 4 studies did not report results.
• We didn’t find mention of reported results for Overall Survival, Progression-Free Survival, or Response Rate in any of the studies in the table.

Safety and Tolerability

Study ID

Grade 3-4 Adverse Events

Treatment Discontinuation

Notable Safety Findings

Merck Sharp & Dohme LLC, 2025a

No mention found

No mention found

No mention found

AVEO Pharmaceuticals, Inc., 2025

No mention found

No mention found

No mention found

Merus N.V., 2025a

No mention found

No mention found

No mention found

Merus N.V., 2025b

No mention found

No mention found

No mention found

GlaxoSmithKline and Merck Sharp & Dohme LLC, 2024a

No mention found

No mention found

No mention found

Inhibrx Biosciences, Inc., 2025

No mention found

No mention found

No mention found

Akeso, 2024

No mention found

No mention found

No mention found

Incyte Corporation and Merck Sharp & Dohme LLC, 2025

No mention found

No mention found

No mention found

Merck Sharp & Dohme LLC and Eisai Inc., 2025a

No mention found

No mention found

No mention found

PDS Biotechnology Corp., 2025

No mention found

No mention found

No mention found

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Summary of findings:

• For 17 studies, we found “No mention found” for all three safety outcomes.
• For 4 studies, we found “No mention found” for all three safety outcomes.
• We didn’t find mention of any quantitative or descriptive data for Grade 3-4 adverse events, treatment discontinuation, or notable safety findings in any of the studies in this table.

Subgroup Analyses

Biomarker-Based Outcomes

• We didn’t find mention of biomarker-based efficacy or safety outcomes in the extracted data.
• Many studies restrict enrollment to biomarker-defined populations, such as Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 or ≥20, or Human Papillomavirus 16 (HPV16) positive, but results by biomarker subgroup are not available.

Regional Variations

• Most industry-sponsored studies are global, with sites in North America, Europe, Asia, and South America.
• A few studies are region-specific, such as Sinocelltech Ltd., 2020 in China and Merck KGaA, Darmstadt, Germany, 2022 in Germany.
• We didn’t find mention of regional efficacy or safety data.

Discussion

• We identified a large number of phase 3, interventional, industry-sponsored trials in metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) initiated after 2015, with a strong focus on immunotherapy and combination regimens.
• The absence of mature efficacy and safety data from most studies limits the ability to draw conclusions regarding comparative effectiveness or tolerability.
• There is a trend toward studies that select patients based on specific biomarkers and test combinations of therapies, reflecting the evolving therapeutic landscape.
• Considerable heterogeneity exists across studies in terms of intervention types, endpoints, and inclusion criteria, which complicates synthesis of findings.

References

Lead Sponsor: GlaxoSmithKline, Sponsor: None\ (2025).NCT06256588: A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Sun Yat-sen University, Collaborator: Fujian Medical University Union Hospital, Collaborator: Guangzhou Panyu Central Hospital, Collaborator: The Central Hospital of Yongzhou, Collaborator: The First People's Hospital of Huaihua, and 6 more\ (2022).NCT05044117: Single-agent Capecitabine as Metronomic Chemotherapy in LAHNSCC (CMHN). NIH

Lead Sponsor: UNICANCER, Collaborator: GORTEC, Collaborator: National Cancer Institute, France, Sponsor: None\ (2024).NCT04747054: Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers. NIH

Lead Sponsor: Exelixis, Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2025).NCT06082167: Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Assiut University, Principal Investigator: doaa abd elaleem alsayed mohamed\ (2021).NCT04780750: Concurent Chemoradiotherapy in Head and Neck Cancers. NIH

Lead Sponsor: Insel Gruppe AG, University Hospital Bern, Collaborator: University of Bern, Sponsor: None\ (2024).NCT02918955: Definitive Chemo-Radiotherapy for Regionally Advanced Head and Neck Cancer With or Without Up-front Neck Dissection. NIH

Lead Sponsor: Merck Sharp & Dohme LLC, Sponsor: None\ (2025).NCT03765918: Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689). NIH

Lead Sponsor: Jiangsu Cancer Institute & Hospital, Collaborator: Affiliated Hospital of Jiangnan University, Collaborator: Changzhou Cancer Hospital of Soochow University, Collaborator: The First Affiliated Hospital with Nanjing Medical University, Collaborator: Northern Jiangsu People's Hospital, and 3 more\ (2015).NCT02485548: Cisplatin Plus Raltitrexed or 5-fluorouracil Concurrent With Radiotherapy for Head and Neck Squamous Cell Cancer. NIH

Lead Sponsor: GlaxoSmithKline, Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2024).NCT04428333: Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: AVEO Pharmaceuticals, Inc., Sponsor: None\ (2025).NCT06064877: A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Merus N.V., Sponsor: None\ (2025).NCT06525220: A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1). NIH

Lead Sponsor: Merus N.V., Sponsor: None\ (2025).NCT06496178: A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients. NIH

Lead Sponsor: GlaxoSmithKline, Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2024).NCT04128696: Study of GSK3359609 and Pembrolizumab in Programmed Death Receptor 1-ligand 1 (PD-L1) Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Sinocelltech Ltd., Sponsor: None\ (2020).NCT04146402: SCT-I10A Plus Standard Chemotherapy in First-line Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Barretos Cancer Hospital, Sponsor: None\ (2019).NCT03815903: Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Inhibrx Biosciences, Inc, Sponsor: None\ (2025).NCT06295731: INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC. NIH

Lead Sponsor: Akeso, Sponsor: None\ (2024).NCT06601335: A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC). NIH

Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC, Sponsor: None\ (2021).NCT03673735: Maintenance Immune Check-point Inhibitor Following Post-operative Chemo-radiation in Subjects With HPV-negative HNSCC. NIH

Lead Sponsor: Merck Sharp & Dohme LLC, Collaborator: Eisai Inc., Sponsor: None\ (2025).NCT05523323: A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010/LEAP-010)-China Extension. NIH

Lead Sponsor: Bicara Therapeutics, Sponsor: None\ (2025).NCT06788990: FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC. NIH

Lead Sponsor: Incyte Corporation, Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2025).NCT03358472: Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304). NIH

Lead Sponsor: Merck Sharp & Dohme LLC, Sponsor: None\ (2025).NCT02358031: A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048). NIH

Lead Sponsor: Merck Sharp & Dohme LLC, Collaborator: Eisai Inc., Sponsor: None\ (2025).NCT04199104: A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010) (KEYNOTE-010). NIH

Lead Sponsor: Sun Yat-sen University, Collaborator: Hunan Cancer Hospital, Collaborator: Guilin Medical University, China, Collaborator: Jiangsu Cancer Institute & Hospital, Collaborator: Xiangya Hospital of Central South University, and 1 more\ (2024).NCT06492460: 2 Courses of Concurrent Cisplatin Chemoradiotherapy After Surgery for High-risk Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: Gruppo Oncologico del Nord-Ovest, Sponsor: None\ (2023).NCT05802290: NIVolumab in Subjects With Recurrent or Metastatic Platinum-refrACTORy SCCHN. NIH

Lead Sponsor: PDS Biotechnology Corp., Sponsor: None\ (2025).NCT06790966: Phase 3 Study of PDS0101 and Pembrolizumab in HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. NIH

Lead Sponsor: AstraZeneca, Collaborator: Innate Pharma, Sponsor: None\ (2025).NCT04590963: Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer. NIH

Lead Sponsor: Lund University Hospital, Sponsor: None\ (2024).NCT06248996: a Multicentre Phase III Study of Risk-based Treatment Intensification With Hyperfractionated Radiotherapy in Head and Neck Cancer Patients. NIH

Lead Sponsor: Bristol-Myers Squibb, Collaborator: Ono Pharmaceutical Co. Ltd, Sponsor: None\ (2023).NCT02741570: Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck. NIH

Lead Sponsor: Institut Català d'Oncologia, Collaborator: Ferrer Internacional S.A., Sponsor: None\ (2019).NCT02715596: Changes in Body Composition After EPA Supplementation in Head and Neck Patients. NIH

Lead Sponsor: All India Institute of Medical Sciences, Principal Investigator: Aman Sharma\ (2022).NCT05187091: The SWOAR Trial Sparing of Swallowing and Aspiration Related Organs at Risk & Submandibular Gland With Intensity Modulated Radiotherapy Versus Standard IMRT in Head and Neck Squamous Cell Carcinomas. NIH

Lead Sponsor: Bristol-Myers Squibb, Sponsor: None\ (2019).NCT03386838: An Immuno-therapy Study of Nivolumab in Combination With Experimental Medication BMS-986205 Compared to Standard of Care EXTREME Regimen in First-line Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck. NIH

Lead Sponsor: AstraZeneca, Sponsor: None\ (2021).NCT02551159: Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer. NIH

Lead Sponsor: Merck KGaA, Darmstadt, Germany, Sponsor: None\ (2022).NCT02383966: Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer. NIH

Lead Sponsor: Nektar Therapeutics, Collaborator: SFJ Pharmaceuticals, Inc., Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2022).NCT04969861: BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36). NIH

Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC, Collaborator: Swiss Cancer Institute, Collaborator: Merck Sharp & Dohme LLC, Sponsor: None\ (2025).NCT05815927: Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer. NIH

Lead Sponsor: National Cancer Institute (NCI), Sponsor: None\ (2025).NCT05063552: Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers. NIH

Lead Sponsor: BioNTech SE, Sponsor: None\ (2025).NCT04534205: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1. NIH

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NCT04199104: A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010) (KEYNOTE-010)

Lead Sponsor: Merck Sharp & Dohme LLC, Collaborator: Eisai Inc., Sponsor: None

NIH·

2025·

Citations unknown

ClinicalTrials

Study Type and Phase

Interventional, Phase 3

Sponsorship Details

Primary Sponsor: Merck Sharp & Dohme LLC

Collaborator: Eisai Inc.

The study is sponsored by the pharmaceutical company Merck Sharp & Dohme LLC, which serves as the lead sponsor. Eisai Inc. is listed as a collaborator, indicating a secondary sponsoring role. The Medical Director (Study Director) is from Merck Sharp & Dohme LLC, and the point of contact for clinical development is also from Merck Sharp & Dohme LLC, confirming their role as the primary industry sponsor of this clinical trial.

Participant Eligibility Criteria

Disease Stage and Metastatic Status: - Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies - Participants with newly-diagnosed HNSCC must be M1/Stage IV

Age Range: - Age: Minimum: 18 Years - No maximum age specified

Performance Status: - Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1

Primary Tumor Location Requirements: - Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx - Primary tumor site of nasopharynx (any histology) or unknown primary tumor (including p16+ unknown primary) are not eligible

Prior Treatment Exclusions: - Has received prior therapy with lenvatinib or pembrolizumab - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) - Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization - Has received prior radiotherapy within 2 weeks of start of study intervention - Had PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC

Critical Exclusion Criteria: - Has disease that is suitable for local therapy administered with curative intent - Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3) or lenvatinib - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Has a known additional malignancy that is progressing or has required active treatment within the past 3 years

Geographical Locations

Total number of countries: 20

Countries where the study is being conducted:

- Australia - Brazil - Canada - China - France - Germany - Hungary - Italy - Japan - Korea, Republic of - Mexico - Peru - Poland - Russian Federation - Spain - Taiwan - Turkey - United Kingdom - United States(1)

Primary Intervention

The primary intervention consists of two comparative treatment arms:

Treatment Arm 1: Pembrolizumab + Lenvatinib - Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles - Lenvatinib, 20 mg (two 10-mg oral capsules) administered QD

Treatment Arm 2: Pembrolizumab + Placebo - Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles - Lenvatinib-matching placebo, oral capsules, administered once daily (QD)

This is a comparative study evaluating whether Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo across multiple outcomes, making this a combination therapy trial versus pembrolizumab monotherapy with placebo control.

A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010) (KEYNOTE-010) (NCT04199104)

Summary

• Status: COMPLETED
• Study Type: INTERVENTIONAL
• Phase: PHASE3
• Allocation: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Purpose: TREATMENT
• Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)
• Enrollment: 511 participants (ACTUAL)
• Start Date: 2020-02-05
• Primary Completion Date: 2023-05-30
• Completion Date: 2025-03-31
• First Posted: 2019-12-13
• Results First Posted: 2024-07-16
• Last Update Posted: 2025-04-23
• Sponsor: Merck Sharp & Dohme LLC

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma.

Hypotheses include:

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR.
• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Conditions & Interventions

Conditions (1)

• Head and Neck Squamous Cell Carcinoma Keywords: head and neck squamous cell carcinoma, pembrolizumab, lenvatinib, PD-L1

Interventions (3)

Eligibility

• Age: Minimum: 18 Years
• Sex: ALL
• Accepts Healthy Volunteers: No

Eligibility Criteria

Inclusion Criteria:

• Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies. Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

• Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx. Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor (including p16+ unknown primary) are not eligible.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

• Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib/placebo, or refrain from heterosexual intercourse during this period
• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib/placebo, whichever occurs last
• Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
• Participants with oropharyngeal cancer must have results from testing of human papillomavirus HPV status.
• Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
• Have adequately controlled blood pressure with or without antihypertensive medications.
• Has adequate organ function.

Exclusion Criteria:

• Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3) or lenvatinib.

• Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.

• Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption.

• Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability.

• Has disease that is suitable for local therapy administered with curative intent.

• Had PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

• Has had major surgery within 3 weeks before to first dose of study interventions.

• Has difficulty swallowing capsules or ingesting a suspension orally or by a feeding tube.

• Has received prior therapy with lenvatinib or pembrolizumab.

• Received last dose of systemic therapy for locoregionally advanced disease less than 6 months before signing consent.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Has received prior radiotherapy within 2 weeks of start of study intervention.

• Has received a live vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

• Received an investigational agent or has used an investigational device within 4 weeks prior to study intervention-administration.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed.

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

• Has an active infection requiring systemic therapy. (e.g., tuberculosis, known viral or bacterial infections, etc.).

• Has a known history of human immunodeficiency virus (HIV) infection.

• Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected) infection.

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.

• Has had an allogenic tissue/solid organ transplant.

• Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.

Locations (152)

Study Officials

• Medical Director (STUDY_DIRECTOR) - Merck Sharp & Dohme LLC

Countries: Australia (3), Brazil (7), Canada (3), China (20), France (5), Germany (8), Hungary (6), Italy (6), Japan (14), Korea, Republic of (6), Mexico (5), Peru (5), Poland (8), Russian Federation (4), Spain (6), Taiwan (5), Turkey (7), United Kingdom (8), United States (26)

Oversight & Regulatory

Data Monitoring Committee: Yes

FDA Regulation

• FDA Regulated Drug: Yes
• FDA Regulated Device: No

Results

Participant Flow

Study Groups: 2

• FG000: Pembrolizumab + Lenvatinib
• FG001: Pembrolizumab + Placebo

Overall Study

Withdrawals

Death

• Pembrolizumab + Lenvatinib: 148

• Pembrolizumab + Placebo: 134 Lost to Follow-up

• Pembrolizumab + Lenvatinib: 1

• Pembrolizumab + Placebo: 1 Withdrawal by Subject

• Pembrolizumab + Lenvatinib: 4

• Pembrolizumab + Placebo: 4 Participants Ongoing

• Pembrolizumab + Lenvatinib: 103

• Pembrolizumab + Placebo: 116

Baseline Characteristics

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Programmed Cell Death Ligand 1 (PD-L1) Tumor Expression

Human Papilloma Virus (HPV) Status

Eastern Cooperative Oncology Group (ECOG Status of 0 vs 1)

Outcome Measures

Primary Outcomes (3)

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 is presented.

Time Frame: Up to ~ 37 months | Units: Percentage of participants | Type: NUMBER

Statistical Analyses

• Method: Miettinen and Nurminen method | P-value: 0.0000019

Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD.

Time Frame: Up to ~ 37 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Regression, Cox | P-value: 0.0001129

Overall Survival (OS)

OS is the time from randomization to death due to any cause.

Time Frame: Up to ~ 37 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Regression, Cox | P-value: 0.8819584

Secondary Outcomes (3)

Duration of Response (DOR)

For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.

Time Frame: Up to ~ 37 months | Units: Months | Type: MEDIAN

Percentage of Participants Who Experienced an Adverse Event (AE)

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Time Frame: Up to ~ 37 months | Units: Percentage of Participants | Type: NUMBER

Percentage of Participants Who Discontinued Study Drug Due to an AE

Time Frame: Up to ~ 34 months | Units: Percentage of Participants | Type: NUMBER

Adverse Events

Reporting Threshold: 5

Time Frame: Up to ~ 37 months

All-cause mortality (ACM) was analyzed in all randomized participants. Safety analyses were conducted in all randomized participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA 26.0 preferred terms “Neoplasm progression”, “Malignant neoplasm progression” and “Disease progression” not related to the drug are excluded.

Event Summary

Serious Adverse Events (200)

Other Adverse Events (64)

Additional Information

PI is Sponsor Employee: No

Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC
• Email: ClinicalTrialsDisclosure@msd.com
• Phone: 1-800-672-6372

IPD Sharing Statement

IPD Sharing: YES

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

URL: https://externaldatasharing-msd.com/

Documents & Links

Study Documents

References (1)

• [1] Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10. (PMID: 33300372) [DERIVED]