Elicit: Interventional Trials in Metastatic Head and Neck SCC (CT, public)
Interventional Trials in Metastatic Head and Neck SCC (CT, public)
Summary
Twenty-one phase 3, interventional, industry-sponsored trials in metastatic head and neck squamous cell carcinoma (SCC) 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.
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 (e.g., 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.
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 the 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)?
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.
- Sponsorship Details:
Identify the primary sponsor of the study, looking for:
Industry sponsor name
Funding source
Sponsoring organization
Participant Eligibility Criteria:
Extract key inclusion and exclusion criteria specific to:
Disease stage (metastatic squamous cell carcinoma)
Age range
Performance status
Prior treatments
Geographical Locations:
List all countries where the study is being conducted.
- Primary Intervention:
Describe the primary intervention in detail, looking for:
- Specific drugs/treatments used
- Combination therapies
- Dosage (if specified)
- Administration method
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 | 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 |
Summary of intervention types:
- Anti-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-PD-1/PD-L1 agents with tyrosine kinase inhibitors: 2 studies.
- Anti-PD-1/PD-L1 agents with or without chemotherapy: 3 studies.
- Anti-EGFR (cetuximab) in combination regimens: 4 studies.
- Chemotherapy as comparator or Standard of Care: 4 studies.
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. Considerable heterogeneity exists across studies in terms of intervention types, endpoints, and inclusion criteria, complicating synthesis of findings.