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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:
ClinicalTrials.gov Identifier:
NCT01866319
First Posted: May 31, 2013
Last Update Posted: November 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
May 28, 2013
May 31, 2013
December 9, 2015
January 14, 2016
November 22, 2017
August 28, 2013
March 24, 2015   (Final data collection date for primary outcome measure)
  • Progression-free Survival (PFS) [ Time Frame: Up to 2 years ]

    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 ]
    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).
  • Progression-free Survival (PFS) [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to 30 months ]
Complete list of historical versions of study NCT01866319 on ClinicalTrials.gov Archive Site
Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]

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)

Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
Not Provided
Not Provided
 
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)
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

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.

Participants assigned to treatment with pembrolizumab could receive up to 2 years of treatment; if participants stopped treatment at 2 years and later experienced progression, they were eligible for a second course of treatment for up to 1 additional year. With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Melanoma
  • Biological: Pembrolizumab
    With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W.
    Other Name: MK-3475
  • Biological: Ipilimumab
    No change with Amendment 05.
  • Experimental: Pembrolizumab Q2W
    Participants receive pembrolizumab, 10 mg/kg intravenously (IV), Q2W for up to 2 years. With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W.
    Intervention: Biological: Pembrolizumab
  • Experimental: Pembrolizumab Q3W
    Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years. With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W.
    Intervention: Biological: Pembrolizumab
  • Active Comparator: Ipilimumab
    Participants receive ipilimumab, 3 mg/kg IV Q3W for a total of 4 doses.
    Intervention: Biological: Ipilimumab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
834
July 2, 2018
March 24, 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
Australia,   Austria,   Belgium,   Canada,   Chile,   Colombia,   France,   Germany,   Israel,   Netherlands,   New Zealand,   Norway,   Spain,   Sweden,   United Kingdom,   United States
 
NCT01866319
3475-006
2012-004907-10 ( EudraCT Number )
Yes
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP