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)

A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 714 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, active-controlled, open-label study of pembrolizumab given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes will be stratified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves event-free survival compared to radiotherapy (with or without cisplatin) given after surgery alone.

Conditions

• Head and Neck Neoplasms

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab 200 mg	200 mg administered IV infusion on Day 1 of each 21-day cycle
RADIATION	Radiotherapy 60 Gray	Low risk participants administered 2 Gray in 30 fractions. Administered using intensity modulated radiation therapy.
RADIATION	Radiotherapy 66 Gray	High risk participants administered 2 Gray in 33 fractions. Administered using intensity modulated radiation therapy.
RADIATION	Radiotherapy 70 Gray	Participants with gross residual disease administered 2 Gray in 35 fractions. Administered using intensity modulated radiation therapy.
DRUG	Cisplatin 100 mg/m^2	100 mg/m\^2 administered by IV infusion on Day 1 of each 21-day cycle

Timeline

• Start date: 2018-12-17
• Primary completion: 2024-07-25
• Completion: 2026-09-10
• First posted: 2018-12-05
• Last updated: 2025-08-20
• Results posted: 2025-08-20

Locations

192 sites across 24 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, France, Germany, Hungary, Ireland, Israel, Japan, Poland, Portugal, Russia, South Korea, Spain, Switzerland, Taiwan, Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study