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)

A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 882 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Participants with recurrent or metastatic (R/M) squamous cell cancer of the head and neck (HNSCC) will be randomly assigned to receive pembrolizumab monotherapy \[pembro mono\], pembrolizumab plus chemotherapy with a platinum-based drug (cisplatin or carboplatin) and 5-Fluorouracil (5-FU) \[pembro combo\], or cetuximab plus a platinum-based drug (cisplatin or carboplatin) and 5-FU \[control\]. The overall primary study hypotheses are as follows in all participants and in participants with Programmed Cell Death Ligand 1 (PD-L1) positive expression defined by Combined Positive Score (CPS) ≥1 and CPS ≥20: 1) pembrolizumab monotherapy prolongs progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by Blinded Independent Central Review (BICR) and prolongs overall survival (OS) compared to standard treatment, and 2) pembrolizumab combination with chemotherapy prolongs PFS per RECIST 1.1 assessed by BICR and prolongs OS compared to standard treatment.

Detailed description

The 12 primary superiority hypotheses will be evaluated by comparing the pembro mono arm or pembro combo arm separately to the control arm, for PFS and OS in all first line (1L) R/M HNSCC participants and in 1L R/M HNSCC participants with positive PD-L1 expression (PD-L1 CPS ≥1 and CPS ≥20). Per protocol, response/progression or adverse events (AEs) that occur during the second pembrolizumab course will not be counted towards efficacy outcome measures or safety outcome measures, respectively.

Conditions

• Recurrent Head and Neck Cancer
• Metastatic Head and Neck Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	Pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to \~2 years).
DRUG	Cisplatin	Cisplatin 100 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum \[up to \~4 months\]).
DRUG	Carboplatin	Carboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum \[up to \~4 months\]).
DRUG	5-FU	5-FU 1000 mg/m\^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum \[up to \~4 months\]).
BIOLOGICAL	Cetuximab	Cetuximab on Day 1 at a dose of 400 mg/m\^2 IV, and then 250 mg/m\^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity

Timeline

• Start date: 2015-03-19
• Primary completion: 2019-02-25
• Completion: 2023-07-19
• First posted: 2015-02-06
• Last updated: 2025-07-18
• Results posted: 2020-02-17

Regulatory

• FDA-regulated drug study