Unresectable Stage III and Stage IV melanoma MedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: PEMBROLIZUMAB
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histologically or cytologically confirmed melanoma 2. Have unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines, not amenable to local therapy 3. Have been untreated for advanced or metastatic disease except as follows: a. BRAF V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) b. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-CTLA-4, anti-PD-1 therapy or Interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation. No other prior adjuvant or neoadjuvant therapy will be allowed 4. Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild type or unknown are eligible) 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 6. Have the presence of at least 1 measurable lesion by CT or MRI per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment. Measurable disease will be verified by central imaging vendor (CIV) prior to randomization. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions. Photographs of cutaneous lesions do not need to be submitted to the CIV 7. Provide a tumor biopsy 8. Have resolution of toxic effect(s) of the most recent prior therapy 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 9. Participant is Male or Female and is at least 18 years of age at the time of signing the informed consent 10. A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period 11. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention 12. The participant provides written informed consent for the study 13. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1 14. Have adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 442 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 348
Exclusion criteria
Exclusion criteria: 1. 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 before the first dose of study treatment 2. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or stage 1, non-ulcerated primary melanoma 480 msec 19. Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multi-gated acquisition scan (MUGA) or echocardiogram 20. Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy 21. Has received prior therapy in the adjuvant setting 22. Has received prior therapy with a mAb, chemotherapy, or an investigational agent or device within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To compare progression-free survival (PFS) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ 2) To compare overall survival (OS);Secondary Objective: 1) To compare objective response rate (ORR) per modified RECIST 1.1 by BICR 2) To assess duration of response (DOR) per modified RECIST 1.1 by BICR 3) To assess safety and tolerability 4) To compare the mean change from baseline in PRO scores in global health status/quality of life (QoL) and physical functioning 5) To compare the time to true deterioration (TTD) in global health status/QoL and physical functioning;Primary end point(s): 1) Progression-free survival (PFS) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, assessed by BICR 2) Overall survival (OS);Timepoint(s) of evaluation of this end point: Interim analysis 1, Futility analysis focused on ORR and PFS: approximately 11-13 months after 1st participant randomized (After first ~200 participants are enrolled and have at least 2 scans performed unless otherwise previously discontinued) Interim analysis 2, PFS and OR: approximately 24 months after firs 1st participant randomized (after enrollment is completed, and ~369 PFS events observed and ~209 OS events observed) Interim analysis 3, PFS and OR: approximately 33 months after 1st participant randomized (~397 PFS events observed, ~263 OS events observed) Final OS analysis: approximately 62 months after 1st participant randomized (~316 OS events) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective response (OR) per modified RECIST 1.1 as assessed by BICR 2) DOR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, assessed by BICR;Timepoint(s) of evaluation of this end point: OR: approximately 11-13 months after 1st participant randomized DOR: will be evaluated on an ongoing basis | — |
Countries
Australia, Brazil, Canada, Chile, China, France, Germany, Israel, Italy, Korea, Republic of, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed