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Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02)

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ClinicalTrials.gov Identifier: NCT04303169
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

Substudy 02C 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 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy 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-7684 Biological: V937 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 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 02C
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 Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Pembrolizumab + MK-7684

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus MK-7684 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

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

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

Experimental: Pembrolizumab + V937

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus V937 intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

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

Biological: V937
Administered via IT injection at a specified dose on specified days
Other Names:
  • Coxsackievirus A21 (CVA21)
  • Formerly known as CAVATAK®
  • CAV21

Experimental: Pembrolizumab

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

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




Primary Outcome Measures :
  1. Percentage of participants who experience an adverse event (AE) [ Time Frame: Up to ~16 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 ~12 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. Pathological complete response (pCR) rate [ Time Frame: Up to ~1.5 months ]
    pCR rate is defined as the proportion of participants with complete absence of viable tumor in the treated tumor bed. Assessments are according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by central review of the pathology results. 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. Near pathological complete response (near pCR) rate [ Time Frame: Up to ~1.5 months ]
    Near pCR is defined as the proportion of participants with >0% but ≤10% of viable tumor cells in the treated tumor bed. Assessments are according to RECIST 1.1 by central review of the pathology results. 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.

  2. Pathological partial response (pPR) rate [ Time Frame: Up to ~1.5 months ]
    pPR rate is defined as the proportion of participants with >10% but ≤50% of the treated tumor bed occupied by viable tumor cells. Assessments are according to RECIST 1.1 by central review of the pathology results. 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.

  3. Recurrence-free survival (RFS) [ Time Frame: Up to ~60 months ]
    RFS is defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Assessments are according to RECIST 1.1 which 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
  • Has been untreated for Stage IIIB, IIIC or IIID melanoma

    • surgical resection of primary melanoma is allowed
    • prior radiotherapy to the primary melanoma is allowed
  • Has provided a baseline tumor biopsy
  • Male participants who receive V937 are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of V937
  • 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, MK-7684, V937, 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 monoclonal antibody (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 only mucosal lesions
  • Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses

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): NCT04303169


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

Locations
Show Show 18 study locations
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: NCT04303169    
Other Study ID Numbers: 3475-02C
2019-003978-22 ( EudraCT Number )
MK-3475-02C ( Other Identifier: Merck )
KEYMAKER-U02 ( Other Identifier: Merck )
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 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.:
programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
Coxsackievirus A21
Intracellular Adhesion Molecule-1 (ICAM-1)
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
Antineoplastic Agents, Immunological
Antineoplastic Agents