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Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01866319
First received: May 28, 2013
Last updated: August 10, 2016
Last verified: August 2016
  Purpose

This study will evaluate the safety and efficacy of 2 different dosing schedules of pembrolizumab (MK-3475), every 2 weeks (Q2W) and every 3 weeks (Q3W), and compare the 2 schedules to treatment with ipilimumab in ipilimumab-naïve participants with unresectable or metastatic melanoma.

With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W.


Condition Intervention Phase
Melanoma
Biological: Pembrolizumab
Biological: Ipilimumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Controlled, Three-Arm, Phase III Study to Evaluate the Safety and Efficacy of Two Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    PFS was defined as the time from randomization to the first documented disease progression, based on blinded independent central radiologic and clinical review using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death due to any cause, whichever occurred first. Disease progression was defined as a 20% or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5mm or the appearance of new lesions.

    Statistical testing was stratified by line of therapy (1st vs. 2nd), programmed cell death ligand 1 (PD-L1) status (positive vs. negative) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1)


  • Overall Survival (OS) [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    OS was defined as the time from randomization to death due to any cause. The reported percentage is estimated using a product-limit (Kaplan-Meier) method for censored data; for participants whose survival data was obtained after the data cut-off date for the interim analysis, data were censored at the date of cut-off (3 March 2015). Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1).


Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    ORR was defined as the percentage of the participants with a best tumor response of complete response (CR) or partial response (PR) based on blinded independent central radiologic and clinical review using RECIST 1.1. CR was defined as disappearance of all target lesions with any pathological lymph nodes having a reduction in short axis to <10 mm. PR was defined as a 30% or greater decrease in the sum of diameters of target lesions.

    Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1)



Enrollment: 834
Study Start Date: August 2013
Estimated Study Completion Date: December 2017
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab Q2W
Participants receive pembrolizumab, 10 mg/kg intravenously (IV), Q2W for up to 2 years. With Amendment 05, all participants will receive a fixed dose of pembrolizumab 200 mg Q3W.
Biological: Pembrolizumab
With Amendment 05, all participants will receive a fixed dose of pembrolizumab 200 mg Q3W
Other Name: MK-3475
Experimental: Pembrolizumab Q3W
Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years. With Amendment 05, all participants will receive a fixed dose of pembrolizumab 200 mg Q3W.
Biological: Pembrolizumab
With Amendment 05, all participants will receive a fixed dose of pembrolizumab 200 mg Q3W
Other Name: MK-3475
Active Comparator: Ipilimumab
Participants receive ipilimumab, 3 mg/kg IV Q3W for a total of 4 doses.
Biological: Ipilimumab
No change with Amendment 05.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Histologically-confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma)
  • At least one measurable lesion
  • No prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (first line) or one prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (second line)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Archived tissue sample or new biopsy sample
  • Female participants of childbearing potential must agree to use effective contraception from Visit 1 to 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug

Exclusion criteria:

  • Prior treatment with ipilimumab or other anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) agent or any anti-programmed cell death (PD-1 or PD-L2) agent
  • Chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or not recovered from adverse events caused by cancer therapeutics administered more than four weeks earlier
  • Currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug
  • Expected to require any other form of systemic or localized antineoplastic therapy while on study
  • On any systemic steroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication
  • History of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration, excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases are eligible
  • Severe hypersensitivity reaction to treatment with another monoclonal antibody
  • Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
  • Active infection requiring systemic therapy
  • Known history of Human Immunodeficiency Virus (HIV)
  • Known history of or positive for Hepatitis B or C
  • Known psychiatric or substance abuse disorder
  • Regular user (including recreational use) of illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
  • Pregnant or breastfeeding, or expecting to conceive, or father children within the projected duration of the study
  • Received a live vaccine within 30 days prior to first dose of study drug
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01866319

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01866319     History of Changes
Other Study ID Numbers: 3475-006  2012-004907-10 
Study First Received: May 28, 2013
Results First Received: December 9, 2015
Last Updated: August 10, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
PD-1
PD1
PD-L1
PDL1

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016