Description:
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.
Title
- Brief Title: Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)
- 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)
Clinical Trial IDs
- ORG STUDY ID:
3475-913
- SECONDARY ID:
MK-3475-913
- SECONDARY ID:
2018-002601-57
- NCT ID:
NCT03783078
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab (MK-3475) | MK-3475 | Pembrolizumab |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
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) | |
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 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective Response Rate (ORR) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | 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
Measure: | Duration of Response (DOR) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Overall Survival (OS) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Overall Survival is the time from the first day of study treatment to death due to any cause. |
Measure: | Percentage of Participants with One or More Adverse events (AEs) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Study Intervention Discontinuation due to AEs |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
- programmed cell death receptor 1 (PD-1)
- programmed cell death ligand 1 (PD-L1)
- anti-PD-1
- anti-PD-L1
- Merkel cell carcinoma
Last Updated
June 18, 2021