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Pembrolizumab plus targeted stereotactic radiotherapy for oligometastatic head and neck squamous cell carcinoma

Pembrolizumab and Radiotherapy for OLigometastatic Squamous Cell Carcinoma of the Head and Neck: a Randomized Phase III Study

PHASE3 · European Organisation for Research and Treatment of Cancer - EORTC · NCT05815927

This study tests whether adding stereotactic ablative radiotherapy (SABR) to pembrolizumab helps people with oligometastatic squamous cell carcinoma of the head and neck stay progression-free longer.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexAll
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC (network)
Drugs / interventionspembrolizumab, radiation
Locations30 sites (Brussels and 29 other locations)
Trial IDNCT05815927 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, multicenter phase III trial enrolling adults with PD-L1 CPS ≥1 and 1–5 oligometastatic head and neck squamous cell carcinomas. Participants are randomized 1:1 to receive pembrolizumab alone or pembrolizumab plus SABR directed to all metastatic lesions, after any definitive treatment to the primary site is completed. The primary outcome is progression-free survival, with treatments delivered per standard pembrolizumab schedules and SABR delivered to all lesions that are technically amenable. Eligibility requires measurable disease, staging within 12 weeks, and that all metastases be suitable for SABR.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed head and neck squamous cell carcinoma, PD-L1 CPS ≥1, 1–5 metastases amenable to SABR, measurable disease, and eligibility for first-line pembrolizumab.

Not a fit: Patients with more than five metastases, PD-L1 CPS <1, or metastases that cannot be treated with SABR are unlikely to gain benefit from the added radiotherapy in this protocol.

Why it matters

Potential benefit: If successful, patients could experience longer periods without cancer progression compared with pembrolizumab alone.

How similar studies have performed: While SABR added to systemic therapy has shown benefit in some oligometastatic cancers, adding SABR to immunotherapy in oligometastatic head and neck cancer has not been widely proven in phase III trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
Main inclusion Criteria:

* Male/female participants who are at least 18 years of age on the day of signing informed consent
* Histologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx, larynx or cervical primary occult and histologically or radiologically confirmed oligometastatic disease. Histological characterization of one metastatic lesion is strongly recommended.
* Patients with synchronous or metachronous oligometastatic disease according to the ESTRO/EORTC consensus (1-5 metastatic lesions, with or without primary/recurrent primary tumour and/or regional disease).
* Amenable to first-line systemic treatment for R/M SCCHN.
* For patients with oropharyngeal cancer: HPV status using p16 IHC evaluated locally.
* PD-L1 CPS of at least 1 as evaluated locally.
* Staging not older than 12 weeks before enrolment.
* All the 1-5 metastases must be amenable to SABR.
* Eligible for treatment with pembrolizumab.
* Have measurable disease based on RECIST 1.1.
* ECOG performance status of 0 to 1.
* Participants must have recovered from all treatment-related toxicities to baseline or grade ≤1, such as from previous radiotherapy, systemic treatment or surgery, and not requiring corticosteroids for managing treatment-related side effects.
* Adequate Organ Function Laboratory Values.
* Before patient registration/enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.

Main exclusion Criteria:

* Nasopharynx, sino-nasal, and salivary gland cancers are excluded.
* In-field progression in \< 6 months after curative intended locoregional irradiation of the head and neck.
* Lesions larger than 6 cm in the largest dimension as measured in the diagnostic CT or MRI scan for lesions outside the brain. Note: bone metastases over 6 cm may be included if in the opinion of the local radiation oncologist they can be treated safely and no inner organ is affected.
* Brain metastases only.
* Has received any previous radiotherapy to any of the 1-5 metastases that would be subject to SABR in the experimental arm unless the investigator agrees to treat only after discussion with the RTQA team.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
* Previously treated brain metastases that are radiologically non-stable. Patients with previously treated brain metastases, i.e., without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention, can participate.
* Known contraindication to imaging tracer or any product of contrast media and MRI contraindications.

Where this trial is running

Brussels and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Oligometastatic Squamous Cell Carcinoma of the Head and Neck, Pembrolizumab, Stereotactic ablative radiotherapy, oligometastatic HNSCC

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.