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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03783078

Collaborator

(none)

Enrollment

Locations

Arm

159.7

Anticipated Duration (Months)

2.5

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Merkel Cell Carcinoma	Drug: Pembrolizumab (MK-3475)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Feb 25, 2019

Actual Primary Completion Date :

Feb 15, 2022

Anticipated Study Completion Date :

Jun 16, 2032

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [Up to approximately 2 years]
The ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by blinded independent central review (BICR). A CR is the disappearance of all target lesions; a PR is at least a 30% decrease in the sum of diameters of target lesions; taking as reference the baseline sum diameters per RECIST 1.1 as assessed by blinded independent central review (BICR).

Secondary Outcome Measures

Duration of Response (DOR) [Up to approximately 2 years]
For participants who demonstrate confirmed CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death from any cause, whichever occurs first.
Progression-Free Survival (PFS) [Up to approximately 2 years]
Progression-Free Survival is defined as the time from the first day of study treatment to the first documented evidence of disease progression by RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
Overall Survival (OS) [Up to approximately 2 years]
Overall Survival is the time from the first day of study treatment to death due to any cause.
Percentage of Participants with One or More Adverse events (AEs) [Up to approximately 2 years]
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Study Intervention Discontinuation due to AEs [Up to approximately 2 years]
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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)
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 that required steroids or has current pneumonitis.
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.

Contacts and Locations

Locations

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