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)

December 20, 2023 updated by: Merck Sharp & Dohme LLC

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

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.

As of amendment 2 (effective 01DEC2022) enrollment into the treatment arm of pembrolizumab and lenvatinib has been discontinued.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle ( Site 4404)
      • Wollstonecraft, New South Wales, Australia, 2065
        • Melanoma Institute Australia ( Site 4402)
  • France
      • Paris, France, 75010
        • A.P.H. Paris, Hopital Saint Louis ( Site 4107)
    • Bouches-du-Rhone
      • Marseille, Bouches-du-Rhone, France, 13005
        • Hopital La Timone ( Site 4103)
    • Gironde
      • Bordeaux, Gironde, France, 33075
        • CHU de Bordeaux- Hopital Saint Andre ( Site 4108)
    • Haute-Garonne
      • Toulouse cedex 9, Haute-Garonne, France, 31059
        • Institut Claudius Regaud ( Site 4105)
    • Ile-de-France
      • Villejuif, Ile-de-France, France, 94800
        • Gustave Roussy ( Site 4101)
    • Rhone
      • Pierre Benite, Rhone, France, 69495
        • Centre Hospitalier Lyon Sud ( Site 4102)
  • Israel
      • Afula, Israel, 1834111
        • HaEmek Medical Center ( Site 4703)
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus-Oncology ( Site 4704)
      • Jerusalem, Israel, 9112001
        • Hadassah Ein Karem Jerusalem ( Site 4702)
      • Petah-Tikva, Israel, 4941492
        • Rabin Medical Center-Oncology ( Site 4705)
      • Ramat Gan, Israel, 5265601
        • Chaim Sheba Medical Center ( Site 4701)
  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 4399)
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia ( Site 4301)
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto IRCCS ( Site 4355)
      • Siena, Italy, 53100
        • Policlinico Le Scotte - A.O. Senese ( Site 4377)
  • South Africa
    • Eastern Cape
      • Port Elizabeth, Eastern Cape, South Africa, 6055
        • CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)
    • Gauteng
      • Pretoria, Gauteng, South Africa, 0181
        • LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)
      • Sandton, Gauteng, South Africa, 2196
        • Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 4863)
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7570
        • Cape Town Oncology Trials ( Site 4864)
  • Spain
    • Cataluna
      • Barcelona, Cataluna, Spain, 08036
        • HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit
    • Madrid, Comunidad De
      • Madrid, Madrid, Comunidad De, Spain, 28034
        • Hospital Universitario Ramón y Cajal ( Site 4802)
  • Switzerland
      • Zurich, Switzerland, 8058
        • Universitaetsspital Zuerich ( Site 4601)
    • Geneve
      • Genève, Geneve, Switzerland, 1211
        • Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 4603)
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)
  • United States
    • California
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute ( Site 4009)
      • Los Angeles, California, United States, 90095
        • UCLA Hematology & Oncology ( Site 4004)
      • Santa Monica, California, United States, 90404
        • Providence Saint John's Health Center ( Site 4010)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado, Anschutz Cancer Pavilion ( Site 4012)
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 4022)
    • New York
      • New York, New York, United States, 10016
        • NYU Clinical Cancer Center ( Site 4002)
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Institute ( Site 4005)
    • Ohio
      • Columbus, Ohio, United States, 43221
        • Martha Morehouse Tower ( Site 4020)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute ( Site 4011)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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
  • 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
  • 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
  • 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
  • Female participants agree to abstain from breastfeeding during the study intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required for each study intervention is:
  • MK-1308A: 120 days
  • MK-3475: 120 days
  • Lenvatinib: 30 days

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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 Names:
  • MK-1308A
Drug: Lenvatinib
Administered via oral capsule at a specified dose on specified days
Other Names:
  • E7080
  • MK-7902
  • LENVIMA®
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.
Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Lenvatinib
Administered via oral capsule at a specified dose on specified days
Other Names:
  • E7080
  • MK-7902
  • LENVIMA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to ~28 months
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.
Up to ~24 months
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.
Up to ~30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to ~30 months
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.
Up to ~30 months
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.
Up to ~30 months
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.
Up to ~30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 3, 2021

Primary Completion (Estimated)

April 3, 2030

Study Completion (Estimated)

April 3, 2030

Study Registration Dates

First Submitted

January 5, 2021

First Submitted That Met QC Criteria

January 5, 2021

First Posted (Actual)

January 7, 2021

Study Record Updates

Last Update Posted (Actual)

December 22, 2023

Last Update Submitted That Met QC Criteria

December 20, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-02D
  • MK-3475-02D (Other Identifier: Merck)
  • KEYMAKER-U02 (Other Identifier: Merck)
  • 2020-003742-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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