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| Name | Class |
|---|---|
| Ono Pharmaceutical Co., Ltd. | INDUSTRY |
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The primary objective of this study is to evaluate the tolerability and safety of a combination of lenvatinib plus nivolumab in participants with hepatocellular carcinoma (HCC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Lenvatinib Plus Nivolumab | Experimental | Participants will receive specified doses of lenvatinib (oral) and nivolumab (intravenous) on specified days. |
|
| Part 2: Lenvatinib Plus Nivolumab | Experimental | If tolerable in Part 1, participants will receive specified doses of lenvatinib and nivolumab on specified days until criteria for discontinuation are met. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenvatinib | Drug | Specified doses will be administered orally on specified days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following hematological or non-hematological toxicities considered to be at least possibly related to lenvatinib and/or nivolumab occurring during Cycle 1: 1) Febrile neutropenia or Grade 4 neutropenia for >7 days; 2) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 3) Grade 4 anemia; 4) Clinical deterioration manifested by drug-related hepatic decompensation; 5) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted; 6) Other Grade 3 toxicity lasting >3 days or Grade 4 non-hematological toxicity of any duration; 7) Grade 2 uveitis, eye pain, or blurred vision that did not respond to topical therapy; 8) Failure to administer 8 or more dose of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. | Cycle 1 (Cycle length = 28 days) |
| Part 1 and Part 2: 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 treatment and until the 30 days after the last dose or until the participants initiated new anticancer therapy, whichever was earlier, was absent at pretreatment (Baseline) or reemerged during treatment, was present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did 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 (in the child of a participant who was exposed to the study drug). | From the first dose of study drug until 30 days after the last dose (up to 53 months) |
| Mean Change From Baseline in Vital Sign: Weight |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review | ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on mRECIST assessed by investigator review. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is less than 10 millimeters [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of diameter of all target lesions without unequivocal progression of all non-target lesions, as compared with Baseline. |
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Inclusion Criteria:
Participants must have confirmed diagnosis of hepatocellular carcinoma (HCC) with any of the following criteria:
Part 1: HCC for which no other appropriate therapy is available; Part 2: No prior systemic therapy for advanced/unresectable HCC
Participants categorized to stage B (not applicable for transarterial chemoembolization), or stage C based on Barcelona Clinic Liver Cancer staging system
Child-Pugh score A
Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 to 1
Age greater than or equal to (>=) 20 years at the time of informed consent
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eisai Trial Site 1 | Kashiwa | Chiba | Japan | |||
| Eisai Trial Site 6 |
A total of 30 participants were enrolled and received treatment. Of these, 6 participants were enrolled in Part 1 and 24 were enrolled in the Part 2.
The study was conducted in two parts (Part 1 and Part 2) between 16 January 2018 and 28 December 2022 at 1 site for Part 1 and 6 sites for Part 2 in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 1, Participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days cycle. Participants with body weight greater than or equal to (>=) 60 kg received lenvatinib 12 mg and participants with body weight less than (<) 60 kg, received lenvatinib 8 mg. |
| FG001 | Part 2: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 2, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days Cycle. Participants with body weight >=60 kg received lenvatinib 12 mg, participants with body weight <60 kg, received lenvatinib 8 mg. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 1, Participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days cycle. Participants with body weight >=60 kg received lenvatinib 12 mg and participants with body weight less than <60 kg, received lenvatinib 8 mg. |
| 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 | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following hematological or non-hematological toxicities considered to be at least possibly related to lenvatinib and/or nivolumab occurring during Cycle 1: 1) Febrile neutropenia or Grade 4 neutropenia for >7 days; 2) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 3) Grade 4 anemia; 4) Clinical deterioration manifested by drug-related hepatic decompensation; 5) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted; 6) Other Grade 3 toxicity lasting >3 days or Grade 4 non-hematological toxicity of any duration; 7) Grade 2 uveitis, eye pain, or blurred vision that did not respond to topical therapy; 8) Failure to administer 8 or more dose of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. | The DLT analysis set included all participants who had completed Cycle 1 without major protocol deviation with at least 75 percent (%) of study drug compliance and at least 2 doses of nivolumab and were assessed for DLT, and participants who had experienced DLT during Cycle 1. | Posted | Count of Participants | Participants | Cycle 1 (Cycle length = 28 days) |
From the first dose of study drug until 30 days after the last dose (up to 53 months)
The safety analysis set included all participants who had received at least 1 dose of study drug.
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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 | Part 1: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 1, Participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days cycle. Participants with body weight >=60 kg received lenvatinib 12 mg and participants with body weight less than <60 kg, received lenvatinib 8 mg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Inquiry Service | Eisai Co., Ltd. | none | 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 | Feb 5, 2021 | Dec 28, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 21, 2023 | Dec 28, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C531958 | lenvatinib |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Nivolumab | Drug | Specified doses will be administered intravenously on specified days. |
|
Mean change from baseline in weight were evaluated.
| Baseline, up to Month 53 |
| Mean Change From Baseline in Vital Sign: Body Mass Index | Mean change from baseline in body mass index were evaluated. | Baseline, up to Month 53 |
| Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation) | Mean change from baseline in SpO2 were evaluated. | Baseline, up to Month 53 |
| Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs) | Treatment-emergent markedly abnormal laboratory value was defined as a postbaseline laboratory value with grade 3 or higher, and with a grade increase from baseline, (that is [i.e.] increasing grade 0 to 3 or higher, grade 1 to 3 or higher, grade 2 to 3 or higher, grade 3 to 4 or 5, grade 4 to 5). Test abnormalities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 =mild; Grade 2 =moderate; Grade 3/Grade 4 =severe/life-threatening, Grade 5 =death. | From the first dose of study drug until 30 days after the last dose (up to 53 months) |
| Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale | Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5=dead. | Baseline, up to Month 53 |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Change from baseline in left ventricular ejection fraction (LVEF) were evaluated by multigated acquisition scan (MUGA) or echocardiogram. | Baseline, up to Month 53 |
| From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months) |
| Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib | Cmax was defined as the maximum plasma concentration for lenvatinib. Cmax was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Tmax: Time to Reach the Cmax for Lenvatinib | Tmax was defined as the time to reach maximum observed plasma concentration (Cmax) for lenvatinib. Tmax was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib | AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 time to last measurable point for lenvatinib. AUC(0-t) was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib | AUC(0-Inf) was defined as the area under the plasma concentration-time curve from 0 to infinity for lenvatinib. AUC(0-Inf) was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib | t1/2 was defined as the terminal elimination phase half-life for lenvatinib. t1/2 was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, CL/F: Apparent Total Clearance for Lenvatinib | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as (Dose/AUC(0-inf))/F. Where AUC(0-inf) is the area under the plasma concentration-time curve from zero to infinity and F is the bioavailability of the drug. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was calculated as (CL/F)/Lambda Z. Where, CL/F is the apparent total clearance and lambda Z is the apparent terminal elimination rate constant. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib | Css,max was defined as the maximum plasma concentration at steady state for lenvatinib. Css,max was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib | Css,min is the minimum plasma concentration at steady state for lenvatinib. Css,min was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib | Tss,Max was defined as the time to reach maximum observed plasma concentration of lenvatinib at steady state. Tss,Max was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib | Rac(Cmax) was calculated as Css,max at Cycle 1 Day 15/Cmax at Cycle 1 Day 1. | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, Rac (AUC0-t): Accumulation Ratio of AUC(0-t) for Lenvatinib | Rac(AUC) was calculated as AUC(0-t) at Cycle 1 Day 15/AUC(0-t) at Cycle 1 Day 1. | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
| Part 1, MRT: Mean Residence Time for Lenvatinib | MRT was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
| Iizuka |
| Fukuoka |
| Japan |
| Eisai Trial Site 3 | Kawasaki | Kanagawa | Japan |
| Eisai Trial Site 4 | Sayama | Osaka | Japan |
| Eisai Trial Site 2 | Chuo-ku | Tokyo | Japan |
| Eisai Trial Site 5 | Chiba | Japan |
| Death |
|
| Physician Decision |
|
| BG001 | Part 2: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 2, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days Cycle. Participants with body weight >=60 kg received lenvatinib 12 mg, participants with body weight <60 kg, received lenvatinib 8 mg. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
|
| Primary | Part 1 and Part 2: 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 treatment and until the 30 days after the last dose or until the participants initiated new anticancer therapy, whichever was earlier, was absent at pretreatment (Baseline) or reemerged during treatment, was present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did 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 (in the child of a participant who was exposed to the study drug). | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. | Posted | Count of Participants | Participants | From the first dose of study drug until 30 days after the last dose (up to 53 months) |
|
|
|
| Primary | Mean Change From Baseline in Vital Sign: Weight | Mean change from baseline in weight were evaluated. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kilogram | Baseline, up to Month 53 |
|
|
|
| Primary | Mean Change From Baseline in Vital Sign: Body Mass Index | Mean change from baseline in body mass index were evaluated. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kilogram per square meter | Baseline, up to Month 53 |
|
|
|
| Primary | Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation) | Mean change from baseline in SpO2 were evaluated. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | percentage of blood oxygen saturation | Baseline, up to Month 53 |
|
|
|
| Primary | Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs) | Treatment-emergent markedly abnormal laboratory value was defined as a postbaseline laboratory value with grade 3 or higher, and with a grade increase from baseline, (that is [i.e.] increasing grade 0 to 3 or higher, grade 1 to 3 or higher, grade 2 to 3 or higher, grade 3 to 4 or 5, grade 4 to 5). Test abnormalities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 =mild; Grade 2 =moderate; Grade 3/Grade 4 =severe/life-threatening, Grade 5 =death. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. | Posted | Count of Participants | Participants | From the first dose of study drug until 30 days after the last dose (up to 53 months) |
|
|
|
| Primary | Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale | Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5=dead. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. | Posted | Count of Participants | Participants | Baseline, up to Month 53 |
|
|
|
| Primary | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Change from baseline in left ventricular ejection fraction (LVEF) were evaluated by multigated acquisition scan (MUGA) or echocardiogram. | Safety analysis set included all participants who received at least 1 dose of lenvatinib or nivolumab. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | %LVEF | Baseline, up to Month 53 |
|
|
|
| Secondary | Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review | ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on mRECIST assessed by investigator review. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is less than 10 millimeters [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of diameter of all target lesions without unequivocal progression of all non-target lesions, as compared with Baseline. | Efficacy analysis set included all participants who received at least 1 dose of lenvatinib and nivolumab. | Posted | Number | 95% Confidence Interval | percentage of participants | From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months) |
|
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|
| Secondary | Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib | Cmax was defined as the maximum plasma concentration for lenvatinib. Cmax was derived by non-compartmental analysis using lenvatinib plasma concentrations. | Pharmacokinetic (PK) analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab, and had evaluable concentration data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| Secondary | Part 1, Tmax: Time to Reach the Cmax for Lenvatinib | Tmax was defined as the time to reach maximum observed plasma concentration (Cmax) for lenvatinib. Tmax was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. | Posted | Median | Full Range | hours | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| Secondary | Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib | AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 time to last measurable point for lenvatinib. AUC(0-t) was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "number analyzed" signifies participants who were evaluable for specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib | AUC(0-Inf) was defined as the area under the plasma concentration-time curve from 0 to infinity for lenvatinib. AUC(0-Inf) was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib | t1/2 was defined as the terminal elimination phase half-life for lenvatinib. t1/2 was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| Secondary | Part 1, CL/F: Apparent Total Clearance for Lenvatinib | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as (Dose/AUC(0-inf))/F. Where AUC(0-inf) is the area under the plasma concentration-time curve from zero to infinity and F is the bioavailability of the drug. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was calculated as (CL/F)/Lambda Z. Where, CL/F is the apparent total clearance and lambda Z is the apparent terminal elimination rate constant. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib | Css,max was defined as the maximum plasma concentration at steady state for lenvatinib. Css,max was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib | Css,min is the minimum plasma concentration at steady state for lenvatinib. Css,min was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
|
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| Secondary | Part 1, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib | Tss,Max was defined as the time to reach maximum observed plasma concentration of lenvatinib at steady state. Tss,Max was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days) |
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|
|
| Secondary | Part 1, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib | Rac(Cmax) was calculated as Css,max at Cycle 1 Day 15/Cmax at Cycle 1 Day 1. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| Secondary | Part 1, Rac (AUC0-t): Accumulation Ratio of AUC(0-t) for Lenvatinib | Rac(AUC) was calculated as AUC(0-t) at Cycle 1 Day 15/AUC(0-t) at Cycle 1 Day 1. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| Secondary | Part 1, MRT: Mean Residence Time for Lenvatinib | MRT was derived by non-compartmental analysis using lenvatinib plasma concentrations. | PK analysis set included all participants who had received at least 1 dose of lenvatinib and nivolumab and had evaluable concentration data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days) |
|
|
|
| 1 |
| 6 |
| 3 |
| 6 |
| 6 |
| 6 |
| EG001 | Part 2: Lenvatinib 12 mg or 8 mg + Nivolumab 240 mg | In Part 2, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with nivolumab 240 mg, infusion, intravenously, Q2W on Days 1 and 15 of each 28 days Cycle. Participants with body weight >=60 kg received lenvatinib 12 mg, participants with body weight <60 kg, received lenvatinib 8 mg. | 18 | 24 | 12 | 24 | 24 | 24 |
| Adrenal insufficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Adrenocorticotropic hormone deficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Liver abscess | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Hyperammonaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Aortic dissection | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Thrombotic microangiopathy | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Adrenocorticotropic hormone deficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 25.1 | Systematic Assessment |
|
| Periorbital inflammation | Eye disorders | MedDRA 25.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Anal erosion | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Angular cheilitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Glossitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Varices oesophageal | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oedema due to hepatic disease | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Thirst | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Contrast media allergy | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Liver abscess | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Scratch | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Face injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Ammonia increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Urinary occult blood positive | Investigations | MedDRA 25.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyperammonaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Vagus nerve disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
|
| Scrotal oedema | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
|
| Scrotum erosion | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Lichen planus | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Platelets: Markedly Abnormal Low |
|
| Leukocytes: Markedly Abnormal Low |
|
| Leukocytes: Markedly Abnormal High |
|
| Lymphocytes: Markedly Abnormal Low |
|
| Lymphocytes: Markedly Abnormal High |
|
| Neutrophils: Markedly Abnormal Low |
|
| Prothrombin international normalized ratio: Markedly Abnormal High |
|
| Alkaline phosphatase: Markedly Abnormal High |
|
| Aspartate aminotransferase: Markedly Abnormal High |
|
| Alanine aminotransferase: Markedly Abnormal High |
|
| Gamma-glutamyl transferase: Markedly Abnormal High |
|
| Bilirubin: Markedly Abnormal High |
|
| Creatinine: Markedly Abnormal High |
|
| Glucose: Markedly Abnormal Low |
|
| Glucose: Markedly Abnormal High |
|
| Albumin: Markedly Abnormal Low |
|
| Cholesterol: Markedly Abnormal High |
|
| Triglycerides: Markedly Abnormal High |
|
| Phosphate: Markedly Abnormal Low |
|
| Sodium: Markedly Abnormal Low |
|
| Sodium: Markedly Abnormal High |
|
| Potassium: Markedly Abnormal Low |
|
| Potassium: Markedly Abnormal High |
|
| Calcium corrected: Markedly Abnormal Low |
|
| Calcium corrected: Markedly Abnormal High |
|
| Magnesium: Markedly Abnormal Low |
|
| Magnesium: Markedly Abnormal High |
|
| Amylase: Markedly Abnormal High |
|
| Lipase: Markedly Abnormal High |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Cycle 1 Day 15 |
|
|