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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,500
200 or 400 mg IV infusion
IV infusion or oral tablets
Oral capsules
300mg or 250mg or 100mg oral tablers
IV Infusion
800mg favezelimab + 200mg pembrolizumab IV Infusion
395 mg or 790 mg SC administration
Arizona Cancer Center at UMC North ( Site 0018)
Tucson, Arizona, United States
RECRUITINGComprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054)
Bakersfield, California, United States
RECRUITINGCalifornia Cancer Associates for Research & Excellence ( Site 0016)
Fresno, California, United States
COMPLETEDProvidence Medical Foundation ( Site 0087)
Fullerton, California, United States
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.
Time frame: Up to approximately 10 years
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.
Time frame: Up to approximately 10 years
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.
Time frame: Up to approximately 10 years
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.
Time frame: Up to approximately 42 months (Up to 90 days after last dose of study treatment)
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.
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Experience Clinically Significant Adverse Events (CSAE)
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.
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Experience Events of Clinical Interest (ECI)
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.
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Discontinue Study Treatment Due to an AE
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.
Time frame: Up to approximately 39 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The Angeles Clinic and Research Institute ( Site 0005)
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGUCLA - Hematology/Oncology - Administrative Office ( Site 0009)
Los Angeles, California, United States
RECRUITINGUniversity of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0076)
Orange, California, United States
COMPLETEDStanford Cancer Center ( Site 0086)
Palo Alto, California, United States
RECRUITINGUCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)
San Francisco, California, United States
RECRUITINGProvidence Saint John's Health Center ( Site 0059)
Santa Monica, California, United States
RECRUITING...and 772 more locations