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Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02)

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ClinicalTrials.gov Identifier: NCT04305054
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : March 16, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:

Substudy 02B is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.

The goal of substudy 02B is to evaluate the safety and efficacy of investigational treatment arms in participants with 1L advanced melanoma and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/pembrolizumab monotherapy.


Condition or disease Intervention/treatment Phase
Melanoma Biological: Pembrolizumab Biological: Vibostolimab Biological: Pembrolizumab/Quavonlimab Drug: Lenvatinib Biological: Favezelimab/Pembrolizumab Drug: ATRA Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 315 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02B
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : April 3, 2030
Estimated Study Completion Date : April 3, 2030

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Pembrolizumab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
 Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®

Biological: Vibostolimab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-7684
Active Comparator: Pembrolizumab
Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
 Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Coformulation Pembrolizumab/Quavonlimab
Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
 Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®

Biological: Pembrolizumab/Quavonlimab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-1308A
Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
 Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®

Biological: Pembrolizumab/Quavonlimab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-1308A

Drug: Lenvatinib
Administered via oral capsule at a specified dose on specified days
Other Names:
  • MK-7902
  • E7080
  • LENVIMA®
Experimental: Coformulation Favezelimab/Pembrolizumab
Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years
 Biological: Favezelimab/Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-4280A
Experimental: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA)
Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).
 Drug: ATRA
Administered via oral capsule at a specified dose on specified days
Experimental: Coformulation Favezelimab/Pembrolizumab + Vibostolimab
Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
 Biological: Vibostolimab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-7684

Biological: Favezelimab/Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Name: MK-4280A


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase [ Time Frame: Up to ~3 weeks ]
    The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported.

  2. Percentage of participants who experience an adverse event (AE): Safety lead-in [ Time Frame: Up to ~3 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE during the safety lead-in period will be reported.

  3. Percentage of participants who discontinue study treatment due to an AE: Safety lead-in [ Time Frame: Up to ~3 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE during the safety lead-in will be reported.

  4. Percentage of participants who experience an adverse event (AE) [ Time Frame: Up to ~28 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.

  5. Percentage of participants who discontinue study treatment due to an AE [ Time Frame: Up to ~24 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.

  6. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) [ Time Frame: Up to ~30 months ]
    ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.


Secondary Outcome Measures :
  1. Duration of Response (DOR) per RECIST 1.1 [ Time Frame: Up to ~30 months ]
    For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologically or cytologically confirmed melanoma
  • Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
  • Has been untreated for advanced disease.
  • Has provided a tumor biopsy
  • If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Lenvatinib: 7 days
  • ATRA: 7 days
  • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent. OR
  • Uses contraception unless confirmed to be azoospermic
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a WOCBP OR
  • Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent . from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • MK-4280A: 120 days
  • MK-1308A: 120 days
  • MK-7684: 50 days
  • MK-3475: 120 days
  • Lenvatinib: 30 days
  • ATRA: 30 days
  • Has adequate organ function
  • Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)

Exclusion Criteria:

  • Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
  • Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has ocular or mucosal melanoma
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has an active infection requiring systemic therapy
  • Has known history of human immunodeficiency virus (HIV)
  • Has history of Hepatitis B or known Hepatitis C virus infection
  • Has a history of (noninfectious) pneumonitis
  • Has a history of active tuberculosis (TB)
  • Has received prior systemic anticancer therapy within 4 weeks prior to randomization
  • Has received prior radiotherapy within 2 weeks of first dose of study intervention
  • Has had major surgery <3 weeks prior to first dose of study intervention
  • Has received a live vaccine within 30 days before the first dose of study intervention
  • Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
  • Has had an allogeneic tissue/solid organ transplant
  • Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
Contacts and Locations
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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): NCT04305054


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04305054    
Other Study ID Numbers: 3475-02B
MK-3475-02B ( Other Identifier: Merck )
KEYMAKER-U02 ( Other Identifier: Merck )
2019-003977-24 ( EudraCT Number )
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: March 16, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme LLC:
programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)
Cytotoxic T lymphocyte associated protein 4 (CTLA4)
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
 Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action