Solid Tumors, Hematologic Malignancies
Conditions
Keywords
PD1, PD-1, PDL1, PD-L1
Brief summary
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.
Interventions
DRUGPembrolizumab
200 or 400 mg IV infusion
DRUGStandard of Care (SOC)
IV infusion or oral tablets
DRUGLenvatinib
Oral capsules
DRUGOlaparib
300mg or 250mg or 100mg oral tablers
DRUGMK-4280
IV Infusion
BIOLOGICALMK-4280A
800mg favezelimab + 200mg pembrolizumab IV Infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on MK-3475-587: * 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. * Demonstrates adequate organ function. * Have resolution of any toxic effect(s) of First Course Phase trial treatment with pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except alopecia) before trial treatment in Second Course Phase is started. If participant received major surgery or radiation therapy of \>30 Gray (Gy), they must have recovered from the toxicity and/or complications of the intervention. * A female participant is eligible to enroll if she is not pregnant, not breastfeeding, and ≥1 of the following conditions applies: A woman of childbearing potential (WOCBP) who agrees to use contraception during the study treatment period and for ≥120 days (corresponding to time needed to eliminate any study combination treatment(s) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity. Additional eligibility criteria for participants who enter dosing with Lenvatinib: * Adequately controlled blood pressure (BP) to \<150/90 mmHg, with or without antihypertensive medications. * For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib. * Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for ≥4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.
Exclusion criteria
-There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Progression Free Survival (PFS) Per Evaluation Criteria Used in the Parent Trial | Up to approximately 10 years | 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 | Up to approximately 10 years | 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) | Up to approximately 42 months (Up to 90 days after last dose of study treatment) | 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) | Up to approximately 40 months (Up to 30 days after last dose of study treatment) | 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. |
| Number of Participants Who Experience Clinically Significant Adverse Events (CSAE) | Up to approximately 40 months (Up to 30 days after last dose of study treatment) | CSAE are AEs associated with lenvatinib treatment and include selected preferred terms from the lenvatinib CSAE preferred term list document. The number of participants who experience an CSAE in this study will be presented. |
| Number of Participants Who Experience Events of Clinical Interest (ECI) | Up to approximately 40 months (Up to 30 days after last dose of study treatment) | ECIs for this study include: 1) An overdose of Sponsor's product, that is not associated with clinical symptoms or abnormal laboratory results or 2) An elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is ≥3X the upper limit of normal (ULN) and an elevated total bilirubin lab value that is ≥2X ULN and, at the same time, an alkaline phosphatase lab value that is \<2X ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing. The number of participants who experience an ECI in this study will be presented. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 39 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be presented. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed