MelanomaPhase 1/2NCT04305041
Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02)
A Phase 1/2 study testing Pembrolizumab, Quavonlimab and Vibostolimab in people with Melanoma, run by Merck Sharp & Dohme LLC at 36 sites in 7 countries.
Trial summary
Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to… 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, Quavonlimab and Vibostolimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 36 sitesin 7 countries
- Study dates
- 26 Jun 2020to 25 Aug 2025
- Phase
- Phase 1/2
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 histologically or cytologically confirmed melanoma
- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
- Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
- Has not received more than 3 lines of therapy for their advanced melanoma
- Has provided a tumor biopsy
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- Male participants who receive lenvatinib or ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed
- Female participant 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, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, whichever occurs last
- Has adequate organ function
- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
Who cannot join
- 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 known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another mAb
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
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- Has an active infection requiring systemic therapy
- Has known history of human immunodeficiency virus (HIV)
- Has known history of hepatitis B
- 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 pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula
- Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Trial locations and contacts
36 sites in 7 countries.
36 sites in 7 countries
United States13 sites
University of Colorado, Anschutz Cancer Pavilion ( Site 1012)
Aurora, Colorado, 80045
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022)
Baltimore, Maryland, 21287
Martha Morehouse Tower ( Site 1020)
Columbus, Ohio, 43221
Duke Cancer Institute ( Site 1005)
Durham, North Carolina, 27710
Inova Schar Cancer Institute ( Site 1011)
Fairfax, Virginia, 22031
West Cancer Center - East Campus ( Site 1014)
Germantown, Tennessee, 38138
University of Texas MD Anderson Cancer Center ( Site 1006)
Houston, Texas, 77030
The Angeles Clinic and Research Institute ( Site 1009)
Los Angeles, California, 90025
UCLA Hematology & Oncology ( Site 1004)
Los Angeles, California, 90095
NYU Clinical Cancer Center ( Site 1002)
New York, New York, 10016
University of Pennsylvania Abramson Cancer Center ( Site 1008)
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University ( Site 1013)
Portland, Oregon, 97239
Providence Saint John's Health Center ( Site 1010)
Santa Monica, California, 90404
France6 sites
Hopital Saint Andre ( Site 1108)
Bordeaux, Gironde, 33075
Hopital La Timone ( Site 1103)
Marseille, Bouches-du-Rhone, 13005
A.P.H. Paris, Hopital Saint Louis ( Site 1107)
Paris, 75010
Centre Hospitalier Lyon Sud ( Site 1102)
Pierre-Bénite, Rhone, 69495
Institut Claudius Regaud ( Site 1105)
Toulouse, Haute-Garonne, 31059
Gustave Roussy ( Site 1101)
Villejuif, Île-de-France Region, 94805
Italy5 sites
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1399)
Milan, 20133
Istituto Europeo di Oncologia ( Site 1301)
Milan, 20141
Istituto Nazionale Tumori Fondazione Pascale ( Site 1302)
Naples, 80131
Istituto Oncologico Veneto IRCCS ( Site 1355)
Padova, 35128
Policlinico Le Scotte - A.O. Senese ( Site 1377)
Siena, 53100
Australia4 sites
Fiona Stanley Hospital ( Site 1401)
Murdoch, Western Australia, 6150
Tasman Oncology Research Pty Ltd ( Site 1403)
Southport, Queensland, 4215
Calvary Mater Newcastle-Medical Oncology ( Site 1404)
Waratah, New South Wales, 2298
Melanoma Institute Australia ( Site 1402)
Wollstonecraft, New South Wales, 2065
Israel4 sites
HaEmek Medical Center ( Site 1703)
Afula, 1834111
Rambam Health Care Campus-Oncology ( Site 1704)
Haifa, 3109601
Hadassah Ein Karem Jerusalem ( Site 1702)
Jerusalem, 9112001
Chaim Sheba Medical Center ( Site 1701)
Ramat Gan, 5265601
Switzerland3 sites
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 1603)
Geneva, Canton of Geneva, 1211
CHUV Centre Hospitalier Universitaire Vaudois ( Site 1602)
Lausanne, Canton of Vaud, 1011
Universitaetsspital Zuerich ( Site 1601)
Zuerich Flughafen, Canton of Zurich, 8058
South Africa1 site
CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE-Clinical Trials Unit ( Site 1865)
Port Elizabeth, Eastern Cape, 6055
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 02A
Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab, Quavonlimab, Vibostolimab, Lenvatinib, ATRA
- Keywords
- receptor tyrosine kinase inhibitor, 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)
- 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
QuavonlimabBiological
Also called MK-1308
Administered via IV infusion at a specified dose on specified days
VibostolimabBiological
Also called MK-7684
Administered via IV infusion at a specified dose on specified days
LenvatinibDrug
Also called MK-7902, LENVIMA®
Administered via oral capsules at a specified dose on specified days
ATRADrug
Also called VESANOID
Administered via oral capsules at a specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Quavonlimab + Vibostolimab | Experimental | Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Receives: Biological: Pembrolizumab; Biological: Quavonlimab; Biological: Vibostolimab |
| Pembrolizumab + Quavonlimab + Lenvatinib | Experimental | Participants will receive pembrolizumab IV plus quavonlimab 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: Quavonlimab; Drug: Lenvatinib |
| Pembrolizumab + all-trans retinoic acid (ATRA) | Experimental | Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years Receives: Biological: Pembrolizumab; Drug: ATRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE was 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 experienced an AE is reported.
Measured: Up to approximately 39 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE was 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 discontinued study treatment due to an AE is reported.
Measured: Up to 35 months
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) With 95% Confidence Interval (CI)
ORR was 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 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 95% CI was reported.
Measured: Up to approximately 59 months
ORR Per RECIST 1.1 With 90% CI
ORR was 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 BICR. RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 90% CI was reported.
Measured: Up to approximately 59 months
Secondary outcomes (1)
Duration of Response (DOR) Per RECIST 1.1
For participants in the analysis population who showed 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 was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurred first. Responses were according to RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Measured: Up to approximately 59 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start26 Jun 2020
- Primary completion25 Aug 2025
- Study completion25 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305041
- Sponsor's protocol ID
- 3475-02A
- Other IDs
- MK-3475-02A, KEYMAKER-U02, 2023-506312-41-00, U1111-1293-5630, 2019-003956-35, 2019, 2023
- Status last verified
- Aug 2026
- First submitted
- 9 Mar 2020
- Last updated
- 1 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf