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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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04305041
Collaborator
(none)
200
Enrollment
33
Locations
3
Arms
117.2
Anticipated Duration (Months)
6.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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 identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 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 02A
Actual Study Start Date :
Jun 26, 2020
Anticipated Primary Completion Date :
Apr 3, 2030
Anticipated Study Completion Date :
Apr 3, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab + Quavonlimab + Vibostolimab

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.

Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®

    • Biological: Quavonlimab
    Administered via IV infusion at a specified dose on specified days
    Other Names:
  • MK-1308

    • Biological: Vibostolimab
    Administered via IV infusion at a specified dose on specified days
    Other Names:
  • MK-7684

    		•
    Experimental: Pembrolizumab + Quavonlimab + Lenvatinib

    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.

    Biological: Pembrolizumab
    Administered via IV infusion at a specified dose on specified days
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Biological: Quavonlimab
    Administered via IV infusion at a specified dose on specified days
    Other Names:
  • MK-1308

    • Drug: Lenvatinib
    Administered via oral capsules at a specified dose on specified days
    Other Names:
  • MK-7902
  • LENVIMA®

    		•
    Experimental: Pembrolizumab + all-trans retinoic acid (ATRA)

    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

    Drug: ATRA
    Administered via oral capsules at a specified dose on specified days
    Other Names:
  • VESANOID

    		•

    Outcome Measures

    Primary Outcome Measures

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

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

    3. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) [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 [Up to ~30 months]

      For participants in the analysis population who show 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

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    • 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)

    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 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Angeles Clinic and Research Institute ( Site 1009) Los Angeles California United States 90025
    2 UCLA Hematology & Oncology ( Site 1004) Los Angeles California United States 90095
    3 Providence Saint John's Health Center ( Site 1010) Santa Monica California United States 90404
    4 University of Colorado, Anschutz Cancer Pavilion ( Site 1012) Aurora Colorado United States 80045
    5 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022) Baltimore Maryland United States 21287
    6 NYU Clinical Cancer Center ( Site 1002) New York New York United States 10016
    7 Duke Cancer Institute ( Site 1005) Durham North Carolina United States 27710
    8 Oregon Health & Science University ( Site 1013) Portland Oregon United States 97239
    9 University of Pennsylvania Abramson Cancer Center ( Site 1008) Philadelphia Pennsylvania United States 19104
    10 West Cancer Center - East Campus ( Site 1014) Germantown Tennessee United States 38138
    11 University of Texas MD Anderson Cancer Center ( Site 1006) Houston Texas United States 77030
    12 Inova Schar Cancer Institute ( Site 1011) Fairfax Virginia United States 22031
    13 Calvary Mater Newcastle-Medical Oncology ( Site 1404) Waratah New South Wales Australia 2298
    14 Melanoma Institute Australia ( Site 1402) Wollstonecraft New South Wales Australia 2065
    15 Tasman Oncology Research Pty Ltd ( Site 1403) Southport Queensland Australia 4215
    16 Fiona Stanley Hospital ( Site 1401) Murdoch Western Australia Australia 6150
    17 Hopital La Timone ( Site 1103) Marseille Bouches-du-Rhone France 13005
    18 Hopital Saint Andre ( Site 1108) Bordeaux Gironde France 33075
    19 Institut Claudius Regaud ( Site 1105) Toulouse cedex 9 Haute-Garonne France 31059
    20 Gustave Roussy ( Site 1101) Villejuif Ile-de-France France 94800
    21 Centre Hospitalier Lyon Sud ( Site 1102) Pierre Benite Rhone France 69495
    22 A.P.H. Paris, Hopital Saint Louis ( Site 1107) Paris France 75010
    23 HaEmek Medical Center ( Site 1703) Afula Israel 1834111
    24 Rambam Health Care Campus-Oncology ( Site 1704) Haifa Israel 3109601
    25 Hadassah Ein Karem Jerusalem ( Site 1702) Jerusalem Israel 9112001
    26 Chaim Sheba Medical Center ( Site 1701) Ramat Gan Israel 5265601
    27 Istituto Oncologico Veneto IRCCS ( Site 1355) Padova Veneto Italy 35128
    28 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1399) Milano Italy 20133
    29 Istituto Europeo di Oncologia ( Site 1301) Milano Italy 20141
    30 Istituto Nazionale Tumori Fondazione Pascale ( Site 1302) Napoli Italy 80131
    31 Policlinico Le Scotte - A.O. Senese ( Site 1377) Siena Italy 53100
    32 CHUV Centre Hospitalier Universitaire Vaudois ( Site 1602) Lausanne Vaud Switzerland 1011
    33 Universitaetsspital Zuerich ( Site 1601) Zuerich Flughafen Zurich Switzerland 8058

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT04305041
    Other Study ID Numbers:
    • 3475-02A
    • MK-3475-02A
    • KEYMAKER-U02
    • 2019-003956-35
    First Posted:
    Mar 12, 2020
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    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)
    Additional relevant MeSH terms:
    Melanoma
    Pembrolizumab
    Lenvatinib

    Study Results

    No Results Posted as of Aug 22, 2022