NCT03783078 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-05-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Objective Response Rate (ORR)

→

outcome · POSTED

Duration of Response (DOR)

→

outcome · POSTED

Progression-free Survival (PFS)

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

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

→

outcome · POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

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.
healthy Volunteers: false
minimum Age: 12 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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)
intervention Names
Drug: Pembrolizumab (MK-3475)
label
Pembrolizumab
type
EXPERIMENTAL

interventions

arm Group Labels
Pembrolizumab
description
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).
name
Pembrolizumab (MK-3475)
other Names
MK-3475
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 55
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Objective Response Rate (ORR)
time Frame
Up to ~34 months

secondary Outcomes

description
For participants who demonstrated 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 was 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 was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was 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 was also considered PD. DOR assessments were based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experienced a confirmed CR or PR was presented.
measure
Duration of Response (DOR)
time Frame
Up to ~58 months
description
Progression-Free Survival was 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 occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 was presented.
measure
Progression-free Survival (PFS)
time Frame
Up to ~58 months
description
OS was defined as the time from the first dose of study treatment until death from any cause.
measure
Overall Survival (OS)
time Frame
Up to ~58 months
description
An AE was 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 was assessed.
measure
Number of Participants With One or More Adverse Events (AEs)
time Frame
Up to ~58 months
description
An AE was 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 discontinued from study treatment due to an AE was assessed.
measure
Number of Participants Who Discontinued From Study Treatment Due to an AE
time Frame
Up to ~27 months

Full study description

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.

Source references

references

citation
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
type
RESULT