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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 : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Melanoma Biological: Pembrolizumab Biological: PegIFN-2b Biological: Ipilimumab Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 293 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 17, 2014
Estimated Primary Completion Date : June 17, 2020
Estimated Study Completion Date : June 17, 2020


Arm Intervention/treatment
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.
Biological: Pembrolizumab
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: PegIFN-2b
Other Names:
  • PegIntron®
  • Sylatron®

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.
Biological: Pembrolizumab
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: Ipilimumab
Other Name: Yervoy®

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.
Biological: Pembrolizumab
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: Ipilimumab
Other Name: Yervoy®

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.
Biological: Pembrolizumab
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: Ipilimumab
Other Name: Yervoy®




Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicities (Part 1A) [ Time Frame: Up to 6 weeks (Cycle 1) ]
  2. Number of participants experiencing adverse events (AEs) [ Time Frame: Up to 27 Months ]
  3. Number of participants discontinuing study drug because of AEs [ Time Frame: Up to 24 Months ]
  4. Progression-free survival (PFS) (Part 2) [ Time Frame: Up to 24 Months ]
  5. Number of participants experiencing grade 3-5 drug-related AEs (Part 1C) [ Time Frame: Up to 27 Months ]
  6. Objective response rate (ORR) (Part 1C) [ Time Frame: Up to 24 Months ]

Secondary Outcome Measures :
  1. ORR using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part 1C) [ Time Frame: Up to 24 Months ]
  2. ORR (Part 2) [ Time Frame: Up to 24 Months ]
  3. Duration of Response (DOR) (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  4. Overall Survival (OS) (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  5. PFS (Parts 1B, 1C) [ Time Frame: Up to 24 Months ]
  6. Number of participants experiencing grade 3-4 AEs [ Time Frame: Up to 27 Months ]
  7. ORR using RECIST 1.1 (Part 1B) [ Time Frame: Up to 24 Months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089685


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

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02089685     History of Changes
Other Study ID Numbers: 3475-029
2013-004072-36 ( EudraCT Number )
First Posted: March 18, 2014    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Melanoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Pembrolizumab
Interferons
Interferon-alpha
Peginterferon alfa-2b
Antibodies, Monoclonal
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs