Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

A Phase 3 Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) as First Line Therapy in Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-913)

This is a single-arm, open-label, multicenter, efficacy, and safety study of pembrolizumab in adult and pediatric participants with previously untreated advanced Merkel Cell Carcinoma (MCC). The primary objective of the trial is to assess the objective response rate, as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following administration of pembrolizumab.

Study Overview

• Status: Completed
• Conditions: Merkel Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab (MK-3475)

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2065
      • Melanoma Institute Australia ( Site 0400)
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle ( Site 0402)
• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital - Horizon Health Network ( Site 0055)
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0051)
• France
  • Calvados
    • Caen, Calvados, France, 14033
      • Hopital de la Cote de Nacre - Caen ( Site 0204)
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • CHU de Bordeaux- Hopital Saint Andre ( Site 0203)
  • Hauts-de-Seine
    • Boulogne-Billancourt, Hauts-de-Seine, France, 92100
      • Hopital Ambroise Pare Boulogne ( Site 0201)
  • Indre-et-Loire
    • Chambray Les Tours, Indre-et-Loire, France, 37170
      • C.H.R.U. de Tours. Hopital Trousseau ( Site 0202)
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille - Hopital Claude Huriez ( Site 0200)
• Italy
  • Milano, Italy, 20141
    • IEO Istituto Europeo di Oncologia ( Site 0223)
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto ( Site 0221)
  • Toscana
    • Siena, Toscana, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese ( Site 0224)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital ( Site 0427)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0264)
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona ( Site 0261)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0263)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General Universitario de Valencia ( Site 0262)
• Sweden
  • Stockholms Lan
    • Solna, Stockholms Lan, Sweden, 171 64
      • Karolinska Universitetssjukhuset Solna ( Site 0281)
  • Vastra Gotalands Lan
    • Goeteborg, Vastra Gotalands Lan, Sweden, 413 45
      • Sahlgrenska Universitetssjukhuset ( Site 0282)
• United States
  • New York
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0006)
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai ( Site 0004)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be male or female and at least 12 years of age, at the time of signing the informed consent/assent.
• Have histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV) as per American Joint Committee on Cancer (AJCC) 8th edition guidelines.

• Have been untreated for advanced or metastatic disease except as follows:

  1. Prior intratumoral therapy will be permitted.
  2. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to Cycle 1 Day 1 (C1D1).
  3. Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy will not be permitted.
• Have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment.
• Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia).
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP)
• OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis).
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky Play-Performance Scale (LPS) ≥50 for pediatric participants up to and including 16 years of age.
• Have adequate organ function

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years with certain exceptions.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis with certain exceptions.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to C1D1.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
• Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
• Has clinically significant cardiac disease within 6 months of C1D1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease. Note: This exclusion criterion does not apply to participants who are diagnosed with unresectable or metastatic MCC.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1.
• Has received radiotherapy within 2 weeks prior to start of study intervention.
• Has received a live vaccine within 30 days prior to C1D1.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to C1D1.
• Has had an allogenic tissue/solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab; Pembrolizumab (MK-3475) 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) intravenous (IV), for up to 35 administrations (approximately 2 years)	Drug: Pembrolizumab (MK-3475); 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) IV up to 35 administrations (approximately 2 years).; Other Names: MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with 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) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by blinded independent central review (BICR) were presented.	Up to ~34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	For participants who demonstrate a confirmed 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) per RECIST 1.1, DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.	Up to ~13 years
Progression-free Survival (PFS)	Progression-Free Survival is defined as the time from the first dose of study treatment to the first documented evidence of disease progression per RECIST 1.1 by BICR 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. PFS as assessed by BICR per RECIST 1.1 will be presented.	Up to ~13 years
Overall Survival (OS)	OS is defined as the time from the first dose of study treatment until death from any cause.	Up to ~13 years
Number of Participants With One or More Adverse Events (AEs)	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE will be assessed.	Up to ~13 years
Number of Participants Who Discontinued From 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue from study treatment due to an AE will be assessed.	Up to ~13 years

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 15, 2024

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2); Merkel cell carcinoma
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma; Carcinoma, Merkel Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-913; MK-3475-913 (Other Identifier: Merck); 2018-002601-57 (EudraCT Number); KEYNOTE-913 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No