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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03783078




Registration number
NCT03783078
Ethics application status
Date submitted
19/12/2018
Date registered
20/12/2018
Date last updated
20/06/2019

Titles & IDs
Public title
Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)
Scientific 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)
Secondary ID [1] 0 0
MK-3475-913
Secondary ID [2] 0 0
3475-913
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Merkel Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab (MK-3475)

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)


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response (OR) - Percentage of participants who have a best response as complete response (CR) or partial response (PR). 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).
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Duration of Response (DOR) - Duration of Response is the time from first response (CR or PR) to subsequent disease progression, or death from any cause, whichever occurs first as assessed by BICR per RECIST 1.1
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) - Progression-Free Survival is the time from the first day of study treatment to the first confirmed disease progression or death due to any cause, whichever occurs first.
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Overall Survival (OS) - Overall Survival is the time from the first day of study treatment to death due to any cause.
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Percentage of Participants with One or More Adverse events (AEs) - 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.
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Study Intervention Discontinuation due to AEs - 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.
Timepoint [5] 0 0
Up to approximately 2 years

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study intervention.

- Has had an allogenic tissue/solid organ transplant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Calvary Mater Newcastle ( Site 0402) - Waratah
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
Canada
State/province [2] 0 0
New Brunswick
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
France
State/province [4] 0 0
Bordeaux
Country [5] 0 0
France
State/province [5] 0 0
Boulogne-Billancourt
Country [6] 0 0
France
State/province [6] 0 0
Caen
Country [7] 0 0
France
State/province [7] 0 0
Chambray Les Tours
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
Italy
State/province [9] 0 0
Milano
Country [10] 0 0
Italy
State/province [10] 0 0
Napoli
Country [11] 0 0
Italy
State/province [11] 0 0
Padova
Country [12] 0 0
Italy
State/province [12] 0 0
Siena
Country [13] 0 0
New Zealand
State/province [13] 0 0
Auckland
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia
Country [17] 0 0
Sweden
State/province [17] 0 0
Goeteborg
Country [18] 0 0
Sweden
State/province [18] 0 0
Solna

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03783078
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03783078