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

NCT ID: NCT03783078

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-25
• Study Completion Date: 2024-02-15

Brief Summary

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.

Conditions

Merkel Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Pembrolizumab (MK-3475)

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

MK-3475

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0006)

New York, New York, United States

Icahn School of Medicine at Mount Sinai ( Site 0004)

New York, New York, United States

Melanoma Institute Australia ( Site 0400)

North Sydney, New South Wales, Australia

Calvary Mater Newcastle ( Site 0402)

Waratah, New South Wales, Australia

Moncton Hospital - Horizon Health Network ( Site 0055)

Moncton, New Brunswick, Canada

Princess Margaret Cancer Centre ( Site 0051)

Toronto, Ontario, Canada

Hopital de la Cote de Nacre - Caen ( Site 0204)

Caen, Calvados, France

CHU de Bordeaux- Hopital Saint Andre ( Site 0203)

Bordeaux, Gironde, France

Hopital Ambroise Pare Boulogne ( Site 0201)

Boulogne-Billancourt, Hauts-de-Seine, France

C.H.R.U. de Tours. Hopital Trousseau ( Site 0202)

Chambray-lès-Tours, Indre-et-Loire, France

CHRU Lille - Hopital Claude Huriez ( Site 0200)

Lille, Nord, France

Azienda Ospedaliera Universitaria Senese ( Site 0224)

Siena, Tuscany, Italy

IEO Istituto Europeo di Oncologia ( Site 0223)

Milan, , Italy

Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)

Napoli, , Italy

Istituto Oncologico Veneto ( Site 0221)

Padua, , Italy

Auckland City Hospital ( Site 0427)

Auckland, , New Zealand

Hospital General Universitario de Valencia ( Site 0262)

Valencia, Valenciana, Comunitat, Spain

Hospital Universitari Vall d Hebron ( Site 0264)

Barcelona, , Spain

Hospital Clinic de Barcelona ( Site 0261)

Barcelona, , Spain

Hospital Universitario La Paz ( Site 0263)

Madrid, , Spain

Karolinska Universitetssjukhuset Solna ( Site 0281)

Solna, Stockholm County, Sweden

Sahlgrenska Universitetssjukhuset ( Site 0282)

Gothenburg, Västra Götaland County, Sweden

Countries

United States; Australia; Canada; France; Italy; New Zealand; Spain; Sweden

References

Mortier L, Villabona L, Lawrence B, Arance A, Butler MO, Beylot-Barry M, Saiag P, Samimi M, Ascierto PA, Spada F, De Pontville M, Maio M, Berrocal A, Espinosa E, Capdevila J, Levin M, Das D, Krepler C, Grebennik D, Chiarion-Sileni V. Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study. Am J Clin Dermatol. 2024 Nov;25(6):987-996. doi: 10.1007/s40257-024-00885-w. Epub 2024 Oct 8.

Reference Type: RESULT

PMID: 39377880 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

https://www.trialsummaries.com/Study/StudyDetails?id=26661&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

MK-3475-913

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-913

Identifier Type: OTHER

Identifier Source: secondary_id

2018-002601-57

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-913

Identifier Type: -

Identifier Source: org_study_id