Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Head and Neck Squamous Cell Cancer

Treatments: Biological: Cetuximab; Drug: Docetaxel; Biological: Pembrolizumab; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02252042

MK-3475-040 (Other Identifier)

2014-001749-26 (EudraCT Number)

3475-040

Details and patient eligibility

About

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 (OS) when compared to standard treatment.

Enrollment: 495 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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495 participants in 2 patient groups

Pembroliziumab

Experimental group

Description:

Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion.

Treatment:

Biological: Pembrolizumab

Standard Treatment

Active Comparator group

Description:

Participants will receive standard treatment of either 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.

Treatment:

Drug: Docetaxel

Drug: Methotrexate

Biological: Cetuximab