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

NCT03783078 | Completed Phase 3 Results FDA Drug

• 4 other identifiers: 3475-913MK-3475-913KEYNOTE-9132018-002601-57
• Study Type: interventional
• Target: 55
• Locations: 8 countries
• Sites: 22

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Duration of Response (DOR)

  Up to ~58 months

• Progression-free Survival (PFS)

  Up to ~58 months

• Overall Survival (OS)

  Up to ~58 months

• Number of Participants With One or More Adverse Events (AEs)

  Up to ~58 months

• Number of Participants Who Discontinued From Study Treatment Due to an AE

  Up to ~27 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

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)

Interventions

Pembrolizumab (MK-3475) 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).

Also known as: MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Prior intratumoral therapy will be permitted.
• 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).
• 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)
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (22)

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

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 0004)

New York, New York, 10029, United States

Location

Melanoma Institute Australia ( Site 0400)

North Sydney, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle ( Site 0402)

Waratah, New South Wales, 2298, Australia

Location

Moncton Hospital - Horizon Health Network ( Site 0055)

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Princess Margaret Cancer Centre ( Site 0051)

Toronto, Ontario, M5G 2M9, Canada

Location

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

Caen, Calvados, 14033, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 0203)

Bordeaux, Gironde, 33000, France

Location

Hopital Ambroise Pare Boulogne ( Site 0201)

Boulogne-Billancourt, Hauts-de-Seine, 92100, France

Location

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

Chambray-lès-Tours, Indre-et-Loire, 37170, France

Location

CHRU Lille - Hopital Claude Huriez ( Site 0200)

Lille, Nord, 59037, France

Location

Azienda Ospedaliera Universitaria Senese ( Site 0224)

Siena, Tuscany, 53100, Italy

Location

IEO Istituto Europeo di Oncologia ( Site 0223)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto ( Site 0221)

Padua, 35128, Italy

Location

Auckland City Hospital ( Site 0427)

Auckland, 1023, New Zealand

Location

Hospital General Universitario de Valencia ( Site 0262)

Valencia, Valenciana, Comunitat, 46014, Spain

Location

Hospital Universitari Vall d Hebron ( Site 0264)

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona ( Site 0261)

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz ( Site 0263)

Madrid, 28046, Spain

Location

Karolinska Universitetssjukhuset Solna ( Site 0281)

Solna, Stockholm County, 171 64, Sweden

Location

Sahlgrenska Universitetssjukhuset ( Site 0282)

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Related Publications (1)

• 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.

  PMID: 39377880 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 20, 2018
• Study Start: February 25, 2019
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2024
• Last Updated: May 28, 2025
• Results First Posted: February 17, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2); AU (2); CA (2); SE (2); IT (4); ES (4); FR (5); NZ (1)