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MelanomaPhase 1/2NCT04700072

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)

A Phase 1/2 study testing Pembrolizumab, Pembrolizumab/Quavonlimab and Lenvatinib in people with Melanoma, run by Merck Sharp & Dohme LLC at 36 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Melanoma
What is being tested?
Pembrolizumab, Pembrolizumab/Quavonlimab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
36 sitesin 8 countries
Study dates
3 May 2021to 17 Oct 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

36 sites in 8 countries.

36 sites in 8 countries

United States9 sites

  • University of Colorado, Anschutz Cancer Pavilion ( Site 4012)

    Aurora, Colorado, 80045

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 4022)

    Baltimore, Maryland, 21287

  • Martha Morehouse Tower ( Site 4020)

    Columbus, Ohio, 43221

  • Duke Cancer Institute ( Site 4005)

    Durham, North Carolina, 27710

  • Inova Schar Cancer Institute ( Site 4011)

    Fairfax, Virginia, 22031

  • The Angeles Clinic and Research Institute ( Site 4009)

    Los Angeles, California, 90025

  • UCLA Hematology & Oncology ( Site 4004)

    Los Angeles, California, 90095

  • NYU Clinical Cancer Center ( Site 4002)

    New York, New York, 10016

  • Providence Saint John's Health Center ( Site 4010)

    Santa Monica, California, 90404

Other trials in United States

France6 sites

  • CHU de Bordeaux- Hopital Saint Andre ( Site 4108)

    Bordeaux, Gironde, 33075

  • Hopital La Timone ( Site 4103)

    Marseille, Bouches-du-Rhone, 13005

  • A.P.H. Paris, Hopital Saint Louis ( Site 4107)

    Paris, 75010

  • Centre Hospitalier Lyon Sud ( Site 4102)

    Pierre-Bénite, Rhone, 69495

  • Institut Claudius Regaud ( Site 4105)

    Toulouse, Haute-Garonne, 31059

  • Gustave Roussy ( Site 4101)

    Villejuif, Île-de-France Region, 94805

Other trials in France

Israel5 sites

  • HaEmek Medical Center ( Site 4703)

    Afula, 1834111

  • Rambam Health Care Campus-Oncology ( Site 4704)

    Haifa, 3109601

  • Hadassah Ein Karem Jerusalem ( Site 4702)

    Jerusalem, 9112001

  • Rabin Medical Center-Oncology ( Site 4705)

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center ( Site 4701)

    Ramat Gan, 5265601

Other trials in Israel

Italy5 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 4399)

    Milan, 20133

  • Istituto Europeo di Oncologia ( Site 4301)

    Milan, 20141

  • Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)

    Naples, 80131

  • Istituto Oncologico Veneto IRCCS ( Site 4355)

    Padova, 35128

  • Policlinico Le Scotte - A.O. Senese ( Site 4377)

    Siena, 53100

Other trials in Italy

South Africa4 sites

  • Cape Town Oncology Trials ( Site 4864)

    Cape Town, Western Cape, 7570

  • CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)

    Port Elizabeth, Eastern Cape, 6055

  • LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)

    Pretoria, Gauteng, 0181

  • Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 4863)

    Sandton, Gauteng, 2196

Other trials in South Africa

Switzerland3 sites

  • Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 4603)

    Geneva, Canton of Geneva, 1211

  • CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)

    Lausanne, Canton of Vaud, 1011

  • Universitaetsspital Zuerich ( Site 4601)

    Zurich, 8058

Other trials in Switzerland

Australia2 sites

  • Calvary Mater Newcastle ( Site 4404)

    Waratah, New South Wales, 2298

  • Melanoma Institute Australia ( Site 4402)

    Wollstonecraft, New South Wales, 2065

Other trials in Australia

Spain2 sites

  • HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Site 4801)

    Barcelona, Catalonia, 08036

  • Hospital Universitario Ramón y Cajal ( Site 4802)

    Madrid, Madrid, Comunidad de, 28034

Other trials in Spain

About this study

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 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.

Conditions
Melanoma
Being tested
Pembrolizumab, Pembrolizumab/Quavonlimab, Lenvatinib
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Medical subject headings
Melanoma, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    Administered via IV infusion at a specified dose on specified days

  • Pembrolizumab/QuavonlimabBiological

    Also called MK-1308A

    Administered via IV infusion at a specified dose on specified days

  • LenvatinibDrug

    Also called MK-7902, E7080, LENVIMA®

    Administered via oral capsule at a specified dose on specified days

Study groups in NCT04700072
Study groupRoleWhat they receive
Coformulation Pembrolizumab/Quavonlimab + LenvatinibExperimentalParticipants 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.
Receives: Biological: Pembrolizumab; Biological: Pembrolizumab/Quavonlimab; Drug: Lenvatinib
Pembrolizumab + LenvatinibExperimentalParticipants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Receives: Biological: Pembrolizumab; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of participants who experience an adverse event (AE)

    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.

    Measured: Up to ~28 months

  2. Percentage of participants who discontinue study treatment due to an AE

    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.

    Measured: Up to ~24 months

  3. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

    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.

    Measured: Up to ~30 months

Secondary outcomes (4)

  1. Duration of Response (DOR) per RECIST 1.1

    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.

    Measured: Up to ~30 months

  2. Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)

    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.

    Measured: Up to ~30 months

  3. Brain metastasis duration of response (BM-DOR) per RANO-BM

    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.

    Measured: Up to ~30 months

  4. Progression-free survival (PFS) per RECIST 1.1

    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.

    Measured: Up to ~30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2021
  2. Study start3 May 2021
  3. Primary completion17 Oct 2025
  4. Study completion17 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04700072
Sponsor's protocol ID
3475-02D
Other IDs
MK-3475-02D, KEYMAKER-U02, 2023-506315-17-00, U1111-1293-5704, 2020-003742-36, 2023
Status last verified
Oct 2025
First submitted
5 Jan 2021
Last updated
28 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab, Pembrolizumab/Quavonlimab and Lenvatinib in people with Melanoma, run by Merck Sharp & Dohme LLC at 36 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, France, Israel, Italy, South Africa and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of participants who experience an adverse event (AE) (time frame: Up to ~28 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04700072.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2025.

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