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| ID | Type | Description | Link |
|---|---|---|---|
| KEYNOTE 523 | Other Identifier | Merck |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This is an open-label Phase 1b study designed to confirm the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with selected solid tumors (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma [excluding uveal melanoma]).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| lenvatinib 20 mg plus pembrolizumab 200 mg | Experimental | Participants with selected tumors will receive oral lenvatinib at a starting dose of 20 milligrams (mg) once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lenvatinib | Drug | lenvatinib capsules |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
The selected tumor types are: non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma)
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eisai Trial Site 1 | Chuo-ku | Tokyo | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36289094 | Derived | Kitano S, Fujiwara Y, Shimizu T, Iwasa S, Yonemori K, Kondo S, Shimomura A, Koyama T, Ebata T, Ikezawa H, Hayata N, Minoshima Y, Miura T, Kubota T, Yamamoto N. A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2022 Dec;90(6):523-529. doi: 10.1007/s00280-022-04480-w. Epub 2022 Oct 26. |
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A total of 11 participants were screened, of which 5 were screen failures and 6 received study treatment.
Participants took part in the study at 1 investigative site in Japan from 12 Jan 2017 to 15 Apr 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lenvatinib 20 mg Plus Pembrolizumab 200 mg | Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 milligram (mg), capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing Dose limiting toxicities (DLTs). In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety analysis set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lenvatinib 20 mg Plus Pembrolizumab 200 mg | Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From the first dose until 30 days after the last dose (approximately 2 years 7 months) |
Baseline up to 30 days after last dose of study drug (approximately 2 years 7 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lenvatinib 20 mg Plus Pembrolizumab 200 mg | Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Subileus | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Inquiry Service | Eisai, Inc. | eisai-chiken_hotline@hhc.eisai.co.jp |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 7, 2020 | Apr 15, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 11, 2019 | Apr 15, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D016889 | Endometrial Neoplasms |
| D002295 | Carcinoma, Transitional Cell |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| C531958 | lenvatinib |
| C582435 | pembrolizumab |
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| pembrolizumab |
| Drug |
pembrolizumab intravenous infusion |
|
| 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 |
| 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. |
| Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 1: 0-24 hours |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 1: 0-24 hours |
| 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 |
| 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 |
| 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 |
| 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 |
| CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 1: 0-24 hours |
| MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours |
| Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 15: 0-24 hours |
| Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 15: 0-24 hours |
| 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 |
| 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 |
| Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 15: 0-24 hours |
| Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab | Cycle 1 Day 15: 0-24 hours |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Lenvatinib 20 mg Plus Pembrolizumab 200 mg | Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 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. | The DLT set included all participants who completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and were assessed for DLT, and participants who experienced DLT during Cycle 1. | Posted | Count of Participants | Participants | 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. | The efficacy analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | 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. | The efficacy analysis set included all participants who received at least 1 dose of study drug. Here overall number analyzed "N" included the participants who had CR or PR. | Posted | Median | 95% Confidence Interval | months | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Cycle 1 Day 1: 0-24 hours |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Median | Full Range | hours | Cycle 1 Day 1: 0-24 hours |
|
|
|
| Secondary | T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Median | Full Range | hours | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Geometric Mean | Standard Deviation | nanogram*hour per milliliter (ng*h/mL) | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | ng*h/mL | Cycle 1 Day 1: 0-24 hours |
|
|
|
| Secondary | Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | liter (L) | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here, overall number analyzed "N" are the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | liter per hour (L/hr) | Cycle 1 Day 1: 0-24 hours |
|
|
|
| Secondary | MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | hours | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Geometric Mean | Standard Deviation | ng/mL | Cycle 1 Day 15: 0-24 hours |
|
|
|
| Secondary | Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Geometric Mean | Standard Deviation | ng/mL | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Median | Full Range | hours | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | ng*h/mL | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | L/h | Cycle 1 Day 15: 0-24 hours |
|
|
|
| Secondary | Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | ng/mL | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Mean | Standard Deviation | ratio | 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. | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Mean | Standard Deviation | ratio | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | 1/hour | 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 | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure. | Posted | Geometric Mean | Standard Deviation | Percentage fluctuation | Cycle 1 Day 15: 0-24 hours |
|
|
|
| Secondary | Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab | The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. | Posted | Count of Participants | Participants | 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 |
|
|
|
| 0 |
| 6 |
| 4 |
| 6 |
| 6 |
| 6 |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Aspergillus infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oedema | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gallbladder enlargement | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Electrocardiogram ST-T change | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypozincaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
|
Not provided
Not provided
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D002294 | Carcinoma, Squamous Cell |
| D006258 | Head and Neck Neoplasms |