Overview

This trial is active, not recruiting.

Condition head and neck squamous cell cancer
Treatments pembrolizumab, methotrexate, docetaxel, cetuximab
Phase phase 3
Targets PD-1, EGFR
Sponsor Merck Sharp & Dohme Corp.
Start date November 2014
End date January 2017
Trial size 466 participants
Trial identifier NCT02252042, 2014-001749-26, 3475-040

Summary

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is that pembrolizumab treatment prolongs overall survival when compared to standard treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle
pembrolizumab MK-3475
(Active Comparator)
Participants receive methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle
methotrexate
docetaxel
cetuximab

Primary Outcomes

Measure
Overall Survival (OS) for All Participants
time frame: Up to approximately 2 years

Secondary Outcomes

Measure
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Cell Death Ligand 1 (PD-L1)-Positive Expression defined by ≥1% Combined Positive Score (CPS)(PD-L1 1% CPS)
time frame: Up to approximately 2 years
Objective Response Rate (ORR) per RECIST 1.1 in All Participants
time frame: Up to approximately 2 years
ORR per RECIST 1.1 in Participants With PD-L1 1% CPS
time frame: Up to approximately 2 years
PFS per RECIST 1.1 for All Participants
time frame: Up to approximately 2 years
OS for Participants With PD-L1 1% CPS
time frame: Up to approximately 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies - Failure of prior platinum therapy - Radiographically-measurable disease based on RECIST 1.1 - Tumor tissue available for PD-L1 biomarker analysis - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate organ function - Female participants of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care - Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care Exclusion Criteria - Disease is suitable for local therapy administered with curative intent - Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization - Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease - Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy - Not recovered from adverse events due to therapy more than 4 weeks earlier - Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1, or not recovered from adverse events due to agents administered more than 4 weeks earlier - Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 - Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast cancers - Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents - Active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active, non-infectious pneumonitis - Active infection requiring systemic therapy - Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial therapy according to local standard of care - Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial - Human immunodeficiency virus (HIV) - Hepatitis B or C - Live vaccine within 30 days of planned start of study therapy

Additional Information

Official title A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..
Location data was received from the National Cancer Institute and was last updated in June 2016.