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Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)

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ClinicalTrials.gov Identifier: NCT04700072
Recruitment Status : Recruiting
First Posted : January 7, 2021
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE January 5, 2021
First Posted Date  ICMJE January 7, 2021
Last Update Posted Date April 29, 2022
Actual Study Start Date  ICMJE May 3, 2021
Estimated Primary Completion Date April 3, 2030   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • 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.
  • 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.
  • 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 ≥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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • 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 (≥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 CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of ≥1 new lesion is also considered PD. 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.
  • Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM) [ Time Frame: Up to ~30 months ]
    BMRR is defined as the percentage of participants in the analysis population who achieve a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids and stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status). Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
  • Brain metastasis duration of response (BM-DOR) per RANO-BM [ Time Frame: Up to ~30 months ]
    For participants in the analysis population who demonstrate a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids, stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status), DOR is defined as the time from first documented CR or PR until PD or death due to any cause, whichever occurs first. Per RANO-BM, PD is defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm in ≥1 lesion. Unequivocal increase in non-target lesions, the appearance of ≥1 new lesion or worsening of clinical status is also considered PD. Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
  • Progression-free survival (PFS) per RECIST 1.1 [ Time Frame: Up to ~30 months ]
    PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)
Official Title  ICMJE 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 02D
Brief Summary

Substudy 02D 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 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Detailed Description Not Provided
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 Melanoma
Intervention  ICMJE
  • 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®
Study Arms  ICMJE
  • Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
    Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
    Interventions:
    • Biological: Pembrolizumab
    • Biological: Pembrolizumab/Quavonlimab
    • Drug: Lenvatinib
  • Experimental: Pembrolizumab + Lenvatinib
    Participants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Lenvatinib
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 5, 2021)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 3, 2030
Estimated Primary Completion Date April 3, 2030   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
  • Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
  • Has not received more than 3 lines of therapy for metastatic melanoma
  • Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period
  • Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, or 30 days after the last dose of lenvatinib, whichever occurs last
  • Has adequate organ function

Exclusion Criteria:

  • Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
  • Has current or history of known leptomeningeal involvement
  • Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
  • Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
  • Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
  • Has an active infection requiring systemic therapy
  • Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
  • Has ocular melanoma
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has known history of immunodeficiency virus (HIV)
  • Has known history of hepatitis B or known hepatitis C virus
  • Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
  • Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
  • Has a history of whole brain irradiation
  • 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 or live attenuated vaccine within 30 days prior to the first dose of study intervention
  • Has had an allogeneic tissue/solid organ transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   France,   Israel,   Italy,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04700072
Other Study ID Numbers  ICMJE 3475-02D
MK-3475-02D ( Other Identifier: Merck )
KEYMAKER-U02 ( Other Identifier: Merck )
2020-003742-36 ( 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 LLC
Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date April 2022

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