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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)

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ClinicalTrials.gov Identifier: NCT04305041
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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
Melanoma Biological: Pembrolizumab Biological: MK-1308 Biological: MK-7684 Drug: Lenvatinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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: Substudy 02A
Actual Study Start Date : June 26, 2020
Estimated Primary Completion Date : April 3, 2030
Estimated Study Completion Date : April 3, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Pembrolizumab + MK-1308 + MK-7684
Participants will receive pembrolizumab intravenously (IV) plus MK-1308 IV plus MK-7684 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: MK-1308
Administered via IV infusion at a specified dose on specified days

Biological: MK-7684
Administered via IV infusion at a specified dose on specified days

Experimental: Pembrolizumab + MK-1308 + Lenvatinib
Participants will receive pembrolizumab IV plus MK-1308 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: MK-1308
Administered via IV infusion at a specified dose on specified days

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 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 [ 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 (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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 submitted prestudy imaging
  • Has not received more than 3 lines of therapy for their advanced melanoma
  • Has provided a tumor biopsy
  • Male participants who receive lenvatinib are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 5 days after the last dose of lenvatinib; for male participants who only receive pembrolizumab, MK-1308, MK-7684, 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, MK-1308, MK-7684 or 30 days after the last dose of lenvatinib, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04305041


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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United States, California
Providence Saint John's Health Center ( Site 1010) Recruiting
Santa Monica, California, United States, 90404
Contact: Study Coordinator    310-582-7455      
United States, Oregon
Oregon Health & Science University ( Site 1013) Recruiting
Portland, Oregon, United States, 97239
Contact: Study Coordinator    971-262-9600      
United States, Tennessee
West Cancer Center - East Campus ( Site 1014) Recruiting
Germantown, Tennessee, United States, 38138
Contact: Study Coordinator    901-683-0055      
Australia, Queensland
Tasman Oncology Research Pty Ltd ( Site 1403) Recruiting
Southport, Queensland, Australia, 4215
Contact: Study Coordinator    +61 7 5613 2480      
France
Hopital La Timone ( Site 1103) Recruiting
Marseille, Bouches-du-Rhone, France, 13005
Contact: Study Coordinator    +33491388591      
Gustave Roussy ( Site 1101) Recruiting
Villejuif, Val-de-Marne, France, 94805
Contact: Study Coordinator    +33142114210      
Israel
Hadassah Ein Karem Jerusalem ( Site 1702) Recruiting
Jerusalem, Yerushalayim, Israel, 9112001
Contact: Study Coordinator    +97226776781      
Switzerland
CHUV Centre Hospitalier Universitaire Vaudois ( Site 1602) Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Study Coordinator    +41213140155      
Universitaetsspital Zuerich ( Site 1601) Recruiting
Zuerich, Zurich, Switzerland, 8091
Contact: Study Coordinator    +41442552588      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04305041    
Other Study ID Numbers: 3475-02A
2019-003956-35 ( EudraCT Number )
MK-3475-02A ( Other Identifier: Merck )
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
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:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action