The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who transition into this extension study.
This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase or 3) Second Course Phase. Each participant will transition to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study. Participants who were in the First Course Phase of study treatment with pembrolizumab or lenvatinib in their parent study will enter the First Course Phase of this study and complete up to 35 doses or more every 3 weeks (Q3W) or 17 doses or more every 6 weeks (Q6W) of study treatment with pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment. Participants who were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase) will enter the Survival Follow-up Phase of this study. Participants who were in the Second Course Phase in their parent study will enter Second Course Phase of this study and complete up to 17 doses Q3W or 8 doses Q6W of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment.
Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses as Q3W or 17 doses Q6W of pembrolizumab (approximately 2 years), if they progress while on the control arm and pembrolizumab is approved for the indication in the country where the potential eligible crossover participant is being evaluated.
Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.
Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase.
Has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
Has received a live vaccine within 30 days prior to the first dose of Second Course Phase trial treatment.
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 the Cycle 1 Day 1 of Second Course Phase.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
Parallel
Pembrolizumab
Drug200 or 400 mg IV infusion
Standard of Care (SOC)
DrugIV infusion or oral tablets
Lenvatinib
DrugOral capsules
Olaparib
Drug300mg or 250mg or 100mg oral tablers
MK-4280
DrugIV Infusion
MK-4280A
Biological/Vaccine800mg favezelimab + 200mg pembrolizumab IV Infusion
Pembrolizumab (+) Berahyaluronidase alfa
Biological/Vaccine395 mg or 790 mg SC administration
17
Treatment groupsSee each treatment group below.
Overall Survival (OS)
OS is defined as the time from randomization or start of study treatment for non-randomized participants (on the parent study) to death due to any cause. Participants without documented death at the time of analysis will be censored at the date of the last known to be alive.
Modified Progression Free Survival (PFS) Per Evaluation Criteria Used in the Parent Trial
Modified PFS is defined as the time from randomization or start of study treatment for nonrandomized participants (on the parent study or this study) to the first documented disease progression per the evaluation criteria used in the parent study based on investigator assessment or death due to any cause, whichever occurs first. The censoring rule is modified that participants without modified PFS events at the time of the analysis will be censored at the date of last known to be alive.
Modified Event Free Survival (EFS) Per Evaluation Criteria Used in the Parent Trial
Modified EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first. The censoring rule is modified that participants without documented modified EFS events at the time of the analysis will be censored at the date of last known to be alive.
Number of Participants Who Experience Serious Adverse Events (SAEs)
A SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience a SAE in this study will be presented.
Number of Participants Who Experience Adverse Events of Special Interest (AEOSI)
AEOSI for this study include selected preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 for the following higher-level terms: Pneumonitis, Colitis, Hepatitis, Nephritis, Adrenal Insufficiency, Hypophysitis, Hyperthyroidism, Hypothyroidism, Thyroiditis, Type 1 Diabetes Mellitus, Severe Skin Reactions Including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): or If grade 3 or higher, Uveitis, Pancreatitis, Myositis, Guillain-Barre Syndrome, Myocarditis, Encephalitis, Sarcoidosis, Infusion Reactions and Myasthenic Syndrome. The number of participants who experience an AEOSI in this study will be presented.
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