Unresectable Stage III and Stage IV melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC, 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); participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor. b. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-CTLA-4, anti-PD-1 therapy or Interferon). Immunotherapy 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 nontarget 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. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib/placebo. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed: a. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR b. Must agree to use contraception unless confirmed to be azoospermic. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception quirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed. 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). OR b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days post pembrolizumab or 30 days post lenvatinib/placebo, whichever occurs last
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 intervention 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 ms. 20. Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram 21. Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy 22. Has received prior therapy in the adjuvant setting 23. Has received prior therapy with a mAb, chemotherapy, or an investigational agent or device
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. 2) To compare overall survival (OS);Secondary Objective: 1) To compare objective response rate (ORR) per RECIST 1.1 by BICR 2) To assess duration of response (DOR) per 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) as assessed by BICR per RECIST 1.1 2) Overall survival (OS);Timepoint(s) of evaluation of this end point: Interim analysis 1, 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 2, PFS and OR: approximately 34 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) as assessed by BICR per RECIST 1.1 2) DOR as assessed by BICR per RECIST 1.1.;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, Austria, Brazil, Canada, Chile, China, France, Germany, Israel, Italy, Korea, Republic of, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
Outcome results
None listed