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Safety and Tolerability of Pembrolizumab (MK-3475) + Pegylated Interferon Alfa-2b and Pembrolizumab+ Ipilimumab in Participants With Advanced Melanoma or Renal Cell Carcinoma (MK-3475-029/KEYNOTE-29)

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ClinicalTrials.gov Identifier: NCT02089685
Recruitment Status : Active, not recruiting
First Posted : March 18, 2014
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE March 14, 2014
First Posted Date  ICMJE March 18, 2014
Last Update Posted Date February 16, 2021
Actual Study Start Date  ICMJE March 17, 2014
Estimated Primary Completion Date March 11, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
  • Number of participants with dose-limiting toxicities (Part 1A) [ Time Frame: Up to 6 weeks (Cycle 1) ]
  • Number of participants experiencing adverse events (AEs) [ Time Frame: Up to 27 Months ]
  • Number of participants discontinuing study drug because of AEs [ Time Frame: Up to 24 Months ]
  • Progression-free survival (PFS) (Part 2) [ Time Frame: Up to 24 Months ]
  • Number of participants experiencing grade 3-5 drug-related AEs (Part 1C) [ Time Frame: Up to 27 Months ]
  • Objective response rate (ORR) (Part 1C) [ Time Frame: Up to 24 Months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2014)
  • Number of participants with dose-limiting toxicities (Part 1) [ Time Frame: Up to 6 weeks (Cycle 1) ]
  • Number of participants experiencing adverse events (AEs) [ Time Frame: Up to 2 years ]
  • Number of participants discontinuing study drug because of AEs [ Time Frame: Up to 2 years ]
  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
  • ORR using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part 1C) [ Time Frame: Up to 24 Months ]
  • ORR (Part 2) [ Time Frame: Up to 24 Months ]
  • Duration of Response (DOR) (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  • Overall Survival (OS) (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  • PFS (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  • Number of participants experiencing grade 3-4 AEs [ Time Frame: Up to 27 Months ]
  • ORR using RECIST 1.1 (Part 1B) [ Time Frame: Up to 24 Months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2014)
  • Number of participants with complete response, very good partial response, moderate partial response, stable disease, or progressive disease [ Time Frame: Up to 2 years ]
  • Objective response rate (ORR) [ Time Frame: Up to 2 years ]
  • Duration of Response (DOR) [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of Pembrolizumab (MK-3475) + Pegylated Interferon Alfa-2b and Pembrolizumab+ Ipilimumab in Participants With Advanced Melanoma or Renal Cell Carcinoma (MK-3475-029/KEYNOTE-29)
Official Title  ICMJE A Phase 1/2 Clinical Trial to Study the Safety and Tolerability of MK-3475 + Pegylated Interferon Alfa-2b (PEG-IFN) and MK-3475 + Ipilimumab (IPI) in Subjects With Advanced Melanoma (MEL) and Renal Cell Carcinoma (RCC) (KEYNOTE 029)
Brief Summary This study is being done to analyze the safety, tolerability, and efficacy of treatment for advanced melanoma (MEL) and renal cell carcinoma (RCC) using combination regimens of pembrolizumab + pegylated interferon alfa-2b (PegIFN-2b) and pembrolizumab + ipilimumab (IPI). The primary hypothesis is that these combinations will be sufficiently well-tolerated to permit continued clinical investigation.
Detailed Description The trial is being done in three parts: Part 1A (MEL and RCC) will define the maximum tolerated dose (MTD)/maximum administered dose (MAD) for the drug combinations; a recommended Phase 2 dose (RP2D) for each combination will be identified. Part 1B (MEL-single arm expansion) will better characterize safety and efficacy and provide preliminary efficacy data for the penbrolizumab + IPI combination in participants with MEL. Part 2 (MEL and RCC) is a randomized portion of the trial and will evaluate preliminary efficacy of the drug combinations given in 6-week cycles for advanced MEL participants. Part 2 was removed from the study with Amendment 3 of the protocol. Part 1C (MEL) is added as the third part of the study with Amendment 3. Part 1C will evaluate safety and efficacy for different doses and dosing intervals for IPI in combination with pembrolizumab in participants with advanced MEL.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Cell Carcinoma
  • Melanoma
Intervention  ICMJE
  • Biological: Pembrolizumab
    Other Names:
    • KEYTRUDA®
    • MK-3475
  • Biological: PegIFN-2b
    Other Names:
    • PegIntron®
    • Sylatron®
  • Biological: Ipilimumab
    Other Name: Yervoy®
Study Arms  ICMJE
  • Experimental: Pembrolizumab + PegIFN-2b
    Participants in Part A receive pembrolizumab intravenously (IV) at assigned dose every 3 weeks + PegIFN-2b subcutaneously (SC) at assigned dose once a week in each 6-week cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: PegIFN-2b
  • Experimental: Pembrolizumab + IPI Q3W
    Participants in Parts 1A and 1B receive pembrolizumab IV at assigned dose every 3 weeks + IPI IV at 1 mg/kg every 3 weeks (Q3W) for a total of two 6-week cycles.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Ipilimumab
  • Experimental: Pembrolizumab + IPI Q6W
    Participants in Part 1C receive pembrolizumab IV at assigned dose every 3 weeks + IPI IV at 50 mg every 6 weeks (Q6W) for a maximum of four 6-week cycles.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Ipilimumab
  • Experimental: Pembrolizumab + IPI Q12W
    Participants in Part 1C receive pembrolizumab IV at assigned dose every 3 weeks + IPI IV at 100 mg every 12 weeks (Q12W) for a maximum of eight 6-week cycles.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Ipilimumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 18, 2017)
293
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2014)
345
Estimated Study Completion Date  ICMJE March 11, 2021
Estimated Primary Completion Date March 11, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of advanced/unresectable or metastatic MEL or RCC (Part 1A only) with predominantly clear cell elements
  • Previously untreated stage III/IV advanced or metastatic MEL (Part 1C only)
  • MEL subjects may be treatment naïve or may have received prior lines of therapy for metastatic disease (Parts 1A and 1B)
  • RCC subjects must have received ≥1 prior line of therapy for metastatic disease (Part 1A)
  • Measurable disease as defined by RECIST 1.1
  • Must provide a tumor sample (archival or newly obtained biopsy) that is adequate for determination of PD (programmed cell death)-Ligand 1 status by immunohistochemistry at a central pathology laboratory prior to enrollment. Note: Adequacy of the tumor sample for PD-Ligand 1 testing is not required prior to enrollment in Part 1C
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate organ function
  • Resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (Parts 1A and 1B) and/or recovered from major surgery or radiation therapy
  • Female participants of childbearing potential must be willing to use adequate contraception during the course of the study through 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 therapy through 120 days after the last dose of study drug

Exclusion Criteria

  • Uveal or ocular MEL
  • 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 drug
  • Prior therapy with an anti-programmed cell death (anti-PD)-1, anti-PD-Ligand 1, anti-PD-Ligand 2 or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab clinical trial. Note: In Part 1C, participants may have received anti-PD-1 and/or anti-Cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) as part of their neo/adjuvant treatment.
  • Has received prior anti-cancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of trial drug or not recovered (≤ Grade 1 or at baseline) from AEs due to previously administered agents (Parts 1A and 1B)
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
  • Known additional malignancy that is progressing or requires active treatment with the exception of early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer or in situ breast cancer that has undergone potentially curative therapy
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Severe hypersensitivity to any pembrolizumab excipients
  • Active autoimmune disease requiring systemic treatment in the past 2 years
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial from screening through 120 days after the last dose of study drug
  • Prior therapy with interferon alfa (in neoadjuvant, adjuvant, or metastatic settings) (Part 1A only)
  • Uncontrolled thyroid dysfunction
  • Uncontrolled diabetes mellitus.
  • Known history of human immunodeficiency virus (HIV)
  • Known history of or is positive for Hepatitis B or Hepatitis C
  • Received a live vaccine within 30 days prior to first dose of study drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Canada,   France,   New Zealand,   United States
 
Administrative Information
NCT Number  ICMJE NCT02089685
Other Study ID Numbers  ICMJE 3475-029
2013-004072-36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date February 2021

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