Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. |
From the first dose until 30 days after the last dose (approximately 2 years 7 months) |
|
Primary |
Number of Participants With Dose-limiting Toxicities |
A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria. |
Cycle 1 (Cycle length=21 days) |
|
Secondary |
Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 |
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. |
From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months |
|
Secondary |
Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 |
DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1. |
From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months. |
|
Secondary |
Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours |
|
Secondary |
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours |
|
Secondary |
T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
|
Secondary |
AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
|
Secondary |
AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours |
|
Secondary |
Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
|
Secondary |
CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours |
|
Secondary |
MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab |
Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1 |
Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab |
Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1. |
Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab |
|
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
|
Secondary |
PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab |
The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100 |
Cycle 1 Day 15: 0-24 hours |
|
Secondary |
Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab |
|
Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months |
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