Phase 3
N=495
Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
Head and Neck Squamous Cell Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02252042 ↗Enrolled (actual)
495
Serious AEs
41.9%
Results posted
Aug 2018
Primary outcome: Primary: Initial Overall Survival (OS) for All Participants — 8.4; 7.1 Months — p=0.03160
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pembrolizumab (Biological); Methotrexate (Drug); Docetaxel (Drug); Cetuximab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Initial Overall Survival (OS) for All Participants |
8.4; 7.1 | 0.03160 sig |
| PRIMARY Updated Final OS for All Participants |
8.4; 6.9 | 0.01605 sig |
| SECONDARY OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS) |
8.7; 7.1 | 0.00493 sig |
| SECONDARY Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants |
2.1; 2.3 | 0.32504 |
| SECONDARY PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
2.2; 2.3 | 0.07736 |
| SECONDARY Objective Response Rate (ORR) Per RECIST 1.1 in All Participants |
14.6; 10.1 | 0.0610 |
| SECONDARY ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
17.3; 9.9 | 0.0171 sig |
| SECONDARY Duration of Response (DOR) Per RECIST 1.1 in All Participants |
18.4; 5.0 | — |
| SECONDARY DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
18.4; 9.6 | — |
| SECONDARY Time to Progression (TTP) Per RECIST 1.1 in All Participants |
2.2; 2.2 | 0.14545 |
| SECONDARY TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
2.7; 2.3 | 0.05851 |
| SECONDARY PFS Per Modified RECIST in All Participants |
3.5; 4.8 | 0.65759 |
| SECONDARY PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
3.6; 4.8 | 0.51982 |
| SECONDARY Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants |
240; 227 | — |
| SECONDARY Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS |
193; 178 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants |
30; 36 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS |
25; 29 | — |
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 (OS) when compared to standard treatment.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02252042). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.