This study will evaluate the safety and efficacy of combination therapy of lenvatinib (E7080/MK-7902) and pembrolizumab following approximately 2 years of pembrolizumab therapy and approximately 2 years or more lenvatinib therapy in adult participants with unresectable or advanced melanoma who have been exposed to anti-programmed cell death ligand 1 (PD-1/L1) agents approved for unresectable or metastatic melanoma. No statistical hypothesis will be tested in this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
103
Administered orally once a day during each 21-day cycle.
Administered as an IV infusion on Day 1 Q3W.
Ironwood Cancer & Research Centers ( Site 0312)
Chandler, Arizona, United States
John Wayne Cancer Institute ( Site 0301)
Santa Monica, California, United States
Advocate Medical Group-Park Ridge ( Site 0313)
Park Ridge, Illinois, United States
Southeast Nebraska Cancer Center ( Site 0316)
Lincoln, Nebraska, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0317)
Dallas, Texas, United States
Inova Schar Cancer Institute ( Site 0314)
Fairfax, Virginia, United States
Melanoma Institute Australia ( Site 0152)
Wollstonecraft, New South Wales, Australia
Princess Alexandra Hospital ( Site 0154)
Woolloongabba, Queensland, Australia
Box Hill Hospital ( Site 0157)
Box Hill, Victoria, Australia
Fiona Stanley Hospital ( Site 0156)
Perth, Western Australia, Australia
...and 13 more locations
Objective Response Rate (ORR)
ORR was defined as the percentage of participants in the analysis population who have a confirmed Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ).
Time frame: Up to approximately 55 months
Progression-free Survival (PFS)
PFS was defined as the time from first day of study intervention to the first documented progressive disease (PD) per RECIST 1.1 by BICR, or death from any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). PFS was calculated using the nonparametric Kaplan-Meier method; participants who did not experience a PFS event were censored at the last disease assessment, or the last assessment before new anticancer treatment if new treatment was initiated.
Time frame: Up to approximately 55 months
Overall Survival (OS)
OS was defined as the time from the first day of study intervention to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was calculated using the nonparametric Kaplan-Meier method.
Time frame: Up to approximately 55 months
Duration of Response (DOR)
For participants who demonstrated a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per RECIST 1.1, DOR was defined as the time from first documented CR or PR until progressive disease (PD) or death from any cause, whichever occurs first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). DOR was calculated using the nonparametric Kaplan-Meier method for censored data.
Time frame: Up to approximately 55 months
Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)
AUC0-inf was defined as the area under the concentration-time curve from time zero extrapolated to infinity. Plasma blood samples collected at specified timepoints, were used to estimate AUC0-inf following Lenvatinib and Pembrolizumab administration. Based on the lenvatinib plasma concentration data obtained on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, a protocol specified population PK analysis was performed to characterize the steady state AUC0-inf of lenvatinib when co-administered with pembrolizumab.
Time frame: Cycle 1 Day 1: 0.5 to 4 hours and 6 to 10 hours postdose; Cycle 1 Day 15: Predose and 2 to 12 hours postdose; Cycle 2 Day 1: Predose, 0.5 to 4 hours, and 6 to 10 hours post-dose (each cycle =21 days)
Number of Participants Who Experience At Least One Adverse Event (AE)
An AE was 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 could therefore have been 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 experienced an AE is presented.
Time frame: Up to approximately 55 months
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE was 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 could therefore have been 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 discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 48 months
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