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

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

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

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.

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

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.