Unresectable Stage III and Stage IV Merkel Cell Carcinoma (MCC) MedDRA version: 21.1 Level: LLT Classification code 10064025 Term: Merkel cell carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Concentration unit: mg/ml milligram(s)/millilitre
C
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Have been untreated for advanced or metastatic disease except as follows: a. Prior intratumoral therapy will be permitted b. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to C1D1 c. Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 therapy will not be permitted 3. 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. Measurable disease will be verified by BICR prior to treatment allocation. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions 4. Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention 5. Be male or female and at least 12 years of age, at the time of signing the informed consent/assent 6. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 7. 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), during the intervention period and for at least 120 days (corresponding to the time needed to eliminate any study intervention) after the last dose of study intervention - 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 - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive 8. Participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the study and agrees to OS data collection until the study endpoints are reached. The participant may also provide consent/assent for future biomedical research; however, the participant may participate in the main study without participating in future biomedical research 9. 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 10. Have adequate organ function Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 y
Exclusion criteria
Exclusion criteria: 1. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years 2. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention 3. 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 4. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients 5. Has an active autoimmune disease that has required systemic treatment in past 2 years 6. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis 7. Has an active infection requiring systemic therapy 8. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority 9. 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 10. Has a known history of active tuberculosis (TB; Bacillus tuberculosis) 11. 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 12. 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 13. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study 14. Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease 15. 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 (eg, CTLA-4, OX-40, CD137) 16. Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1 17. Has received radiotherapy within 2 weeks prior to start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids 18. Has received a live vaccine within 30 days prior to C1D1 19. 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 20. Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the objective response rate (ORR), as assessed by blinded independent central review (BICR) 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);Secondary Objective: 1) To assess duration of response (DOR), as assessed by BICR per 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 2) To assess the progression-free survival (PFS), as assessed by BICR per 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 3) To assess overall survival (OS) following administration of pembrolizumab 4) To assess safety and tolerability of treatment with pembrolizumab;Primary end point(s): Objective Response (OR), definded as complete response ro partial response.;Timepoint(s) of evaluation of this end point: approx. 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of Response (DOR): For participants who demonstrate confirmed CR or PR, the time from first documented evidence of CR or PR until disease progression or death from any cause, whichever occurs first 2) Progression-free Survival (PFS): The time from the first day of study treatment to the first confirmed disease progression BICR documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first 3) Overall Survival (OS): The time from the first day of study treatment to death due to any cause 4) Adverse events (AEs) 5) Study intervention discontinuation due to AEs;Timepoint(s) of evaluation of this end point: approx. 13 years | — |
Countries
Australia, Canada, France, Italy, New Zealand, Spain, Sweden, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck
Outcome results
None listed