Study of Lenvatinib in Combination With Everolimus in Rec... | NCT03245151 | Trialant
NCT03245151
Sponsor
Eisai Inc.
Status
Completed
Last Update Posted
Aug 30, 2023Actual
Enrollment
64Actual
Phase
Phase 1Phase 2
Conditions
Recurrent and Refractory Solid Tumors
Interventions
Lenvatinib
Everolimus
Countries
United States
Canada
Protocol Section
Identification Module
NCT ID
NCT03245151
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
E7080-A001-216
Secondary IDs
Not provided
Brief Title
Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors
Official Title
A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors
Acronym
Not provided
Organization
Eisai Inc.INDUSTRY
Status Module
Record Verification Date
Nov 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 16, 2017Actual
Primary Completion Date
Sep 30, 2022Actual
Completion Date
Sep 30, 2022Actual
First Submitted Date
Aug 3, 2017
First Submission Date that Met QC Criteria
Aug 7, 2017
First Posted Date
Aug 10, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Aug 7, 2023
Results First Submitted that Met QC Criteria
Aug 7, 2023
Results First Posted Date
Aug 30, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 7, 2023
Last Update Posted Date
Aug 30, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Eisai Inc.INDUSTRY
Collaborators
Name
Class
Merck Sharp & Dohme LLC
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of lenvatinib administered in combination with everolimus once daily to pediatric participants with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design, will be conducted to estimate the antitumor activity of lenvatinib in combination with everolimus in pediatric participants with selected recurrent/refractory solid tumors including Ewing sarcoma, rhabdomyosarcoma, and high grade glioma (HGG) using objective response rate (ORR) at Week 16 as the outcome measure.
Phase 1: Phase 1; Recurrent or refractory solid tumors
Experimental
During Phase 1 (Treatment Phase: 1 cycle; 28 days of treatment), utilizing a rolling 6 design, participants with recurrent or refractory solid tumors will receive escalating doses of lenvatinib in combination with everolimus for determination of the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Participants who complete 1 cycle of treatment will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
Drug: Lenvatinib
Drug: Everolimus
Phase 2: Cohort 1, Ewing sarcoma
Experimental
During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory Ewing sarcoma (Cohort 1) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1. Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
Drug: Lenvatinib
Drug: Everolimus
Phase 2: Cohort 2, Rhabdomyosarcoma
Experimental
During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory rhabdomyosarcoma (Cohort 2) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks of treatment). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Lenvatinib
Drug
oral hard capsules containing 1 mg, 4 mg, or 10 mg lenvatinib, or an extemporaneous suspension
Phase 1: Phase 1; Recurrent or refractory solid tumors
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus
MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.
Cycle 1 (Each cycle was of 28 days)
Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus
The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.
Cycle 1 (Each cycle was of 28 days)
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
Secondary Outcomes
Measure
Description
Time Frame
Phase 1: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria
≥2 years and <18 years of age for enrolment in Phase 1 or ≥2 years and ≤21 years of age for enrolment in Phase 2.
Recurrent or refractory solid tumors
Phase 1: All solid tumors (measurable or evaluable disease), including primary central nervous system (CNS) tumors; exclusion of hepatoblastoma and lymphomas. Participants with diffuse intrinsic pontine glioma, optic pathway glioma, or pineal tumors with elevated tumor markers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [ß-hCG][or human chorionic gonadotropin [hCG])do not require histological or cytological confirmation of diagnosis
Phase 2: Ewing sarcoma, Rhabdomyosarcoma, High Grade Glioma (HGG) (all must have measurable disease); exclusion of Diffuse Intrinsic Pontine Glioma
Histologically or cytologically confirmed diagnosis
Measurable disease that meets the following criteria (Phase 2):
RECIST 1.1 (for all tumor types except HGG): At least 1 lesion of ≥1.0 cm in the longest diameter for a non lymph node or ≥1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computed tomography /magnetic resonance imaging (CT/MRI)
Response Assessment in Neuro-Oncology (RANO) for high grade glioma (HGG): At least one lesion must be measurable as defined as a bi dimensionally contrast enhancing lesion with clearly defined margins by CT or MRI scan, with a minimal diameter of 1 cm, and visible on 2 axial slices which are preferably at most 5 mm apart with 0 mm skip
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
Karnofsky performance score ≥50 for participants>16 year of age and Lansky play score ≥50 for participants ≤16 years of age. Neurologic deficits in participants with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Prior Therapy
Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy
Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil counts): ≥7 days after the last dose of agent
Monoclonal antibodies: ≥21 days or 3 half-lives (whichever is shorter) of the antibody must have elapsed after the last dose of a monoclonal antibody (including checkpoint inhibitors). Toxicity related to prior antibody therapy must be recovered to Grade ≤1
Corticosteroids: If used to modify immune adverse events related to prior therapy, ≥14 days must have elapsed since last dose of corticosteroid. Participants receiving corticosteroids, who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment, are not eligible
Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥21 days after the completion of interleukins, interferons or cytokines (other than hematopoietic growth factors)
Stem cell infusions (with or without total body irradiation): Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor leukocytes infusion or boost infusion: ≥84 days after infusion and no evidence of graft versus host disease; Autologous stem cell infusion including boost infusion: ≥42 days
Cellular Therapy: ≥42 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer cells, dendritic cells, etc)
Radiotherapy (XRT)/External Beam Irradiation including Protons: ≥14 days after local XRT; ≥150 days after total body irradiation, craniospinal XRT or if radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow radiation.
Radiopharmaceutical therapy: ≥42 days after systemically administered therapy.
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received prior exposure to lenvatinib; May have previously progressed on an mTOR inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only); Must not have received prior VEGF/VEGFR-targeted therapy in combination with an mTOR inhibitor (For Phase 2 only)
Adequate bone marrow function for participants with solid tumors without known bone marrow involvement
Adequate bone marrow function for participants with known bone marrow metastatic disease
Adequate renal function
Adequate liver function
Adequate cardiac function
Adequate neurologic function
Adequate blood pressure (BP) control with or without antihypertensive medications
Adequate coagulation
Adequate pancreatic function
Adequate metabolic function
Adequate glycemic control
Participants must have a minimum body surface area (BSA) of 0.6 m^2 at study entry.
Exclusion Criteria
Participants who have had or are planning to have the following invasive procedures
Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment
Central line placement or subcutaneous port placement is not considered major surgery. External central lines must be placed at least 3 days prior to enrollment and subcutaneous ports must be placed at least 7 days prior to enrollment
Fine needle aspirate within 7 days prior to enrolment
Surgical or other wounds must be adequately healed prior to enrolment
For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy
Participants who have non-healing wound, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrolment
Participants having an active infection requiring systemic therapy.
Participants with a known history of active hepatitis B (defined as hepatitis B surface antigen reactive or hepatitis B virus- deoxyribonucleic [DNA] detected) or known active hepatitis C virus (HCV, defined as HCV- Ribonucleic acid [RNA] detected). Note: No testing for hepatitis B and hepatitis C is required unless mandated by the local health authority.
Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing is required at screening only when mandated by the local health authority
Clinical evidence of nephrotic syndrome prior to enrolment
Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrolment
Thrombotic/ thromboembolic event requiring systemic anticoagulation within 90 days prior to enrollment
Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment for Participants with HGG
Diagnosis of lymphoma
Radiographic evidence of major blood vessel invasion/infiltration.
Evidence of untreated CNS metastases (exception: participants with primary CNS tumors and leptomeningeal disease)
Participants who are currently receiving enzyme-inducing anticonvulsants
Participants chronically receiving strong cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (P-gp) inhibitors or inducers within 7 days prior to study enrollment
Females who are breastfeeding or pregnant. For females of childbearing potential, a negative screening pregnancy test must be obtained within 72 hours before the first dose of study drug
Males who have not had a successful vasectomy (confirmed azoospermia) or if they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 7 days after lenvatinib discontinuation or 4 weeks after discontinuation of everolimus). No sperm donation is allowed during the study period and for 7 days after lenvatinib discontinuation or 4 weeks after discontinuation of everolimus.](streamdown:incomplete-link)
Dela Cruz FS, Fox E, DuBois SG, Friedman GK, Croop JM, Kim A, Morgenstern DA, Balis FM, Macy ME, Pressey JG, Watt T, Krystal JI, Vo KT, Mody R, Laetsch TW, Weigel BJ, O'Hara K, He CS, Aluri J, Okpara CE, Glade Bender JL. A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric and Young Adult Solid Tumors. Pediatr Blood Cancer. 2025 Jul;72(7):e31692. doi: 10.1002/pbc.31692. Epub 2025 May 1.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 86 participants were screened, out of which 64 were enrolled and 9 participants completed the study.
Recruitment Details
Participants took part in the study at 24 investigative sites in the United States and Canada from 16 November 2017 to 30 September 2022.
Participants with recurrent or refractory solid tumors received lenvatinib 8 milligram per square meter (mg/m^2), capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of disease progression (PD), clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Aug 16, 2021
Aug 7, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Palau
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Lenvatinib
Drug: Everolimus
Phase 2: Cohort 3, High Grade Glioma (HGG)
Experimental
During Phase 2 (four 28-day cycles [up to 16 weeks of treatment]), utilizing Simon's optimal 2-stage design, participants with recurrent or refractory HGG (Cohort 3) will receive the RP2D of lenvatinib in combination with everolimus determined in Phase 1 (1 cycle; 4 weeks). Participants who discontinue study treatment before completing 4 cycles will transition to the Off-treatment Visit. Participants who complete 4 cycles will transition to the Extension Phase, in which they will continue to receive the same study treatment in 28-day cycles.
Drug: Lenvatinib
Drug: Everolimus
Phase 2: Cohort 1, Ewing sarcoma
Phase 2: Cohort 2, Rhabdomyosarcoma
Phase 2: Cohort 3, High Grade Glioma (HGG)
Everolimus
Drug
2 mg, 3 mg, or 5 mg tablets for oral suspension
Phase 1: Phase 1; Recurrent or refractory solid tumors
Phase 2: Cohort 1, Ewing sarcoma
Phase 2: Cohort 2, Rhabdomyosarcoma
Phase 2: Cohort 3, High Grade Glioma (HGG)
From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
Phase 2: Objective Response Rate (ORR) at Week 16
ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.
Week 16
From the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 16.5 months)
Phase 2: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
From the date of the first dose of study drug to the date of first documentation of disease progression or death, which ever occurred first (up to 6.5 months)
Phase 1: Disease Control Rate (DCR)
DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration >=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
Phase 2: Disease Control Rate (DCR)
DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [>=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
Phase 1: Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
Phase 2: Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
Phase 1: Duration of Response (DOR)
DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 16.5 months)
Phase 2: Duration of Response (DOR)
DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 6.5 months)
Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])
AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)
Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)
Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib
Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.
Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)
Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
Phoenix
Arizona
85016
United States
Loma Linda University Medical Center
Loma Linda
California
92350
United States
Miller Children's and Women's Hospital
Long Beach
California
90806
United States
Children's Hospital of Los Angeles
Los Angeles
California
90027
United States
Southern California Permanente Medical Group
Los Angeles
California
90027
United States
Kaiser Permenente
Oakland
California
94611
United States
Children's Hospital of Orange County
Orange
California
92868
United States
UCSF Medical Center at Mission Bay - Pediatric Oncology
San Francisco
California
94158
United States
Children's Hospital Colorado
Aurora
Colorado
80045
United States
Nemours/ Alfred I. duPont Hospital for Children
Wilmington
Delaware
19803
United States
Children's National Medical Center
Washington D.C.
District of Columbia
20010
United States
Golisano Children's Hospital of Southwest Florida
Fort Myers
Florida
33908
United States
University of Florida
Gainesville
Florida
32610
United States
Nicklaus Children's Hospital
Miami
Florida
33155
United States
Kapi'olani Medical Center
Honolulu
Hawaii
96826
United States
St Jude Midwest Affiliate
Peoria
Illinois
61637
United States
Riley Hospital for Children - Indiana University
Indianapolis
Indiana
46202
United States
University of Louisville and Norton Children's Hospital
Louisville
Kentucky
40202
United States
Johns Hopkins
Baltimore
Maryland
21287
United States
Dana-Farber Cancer Institute
Boston
Massachusetts
02215
United States
CS Mott Children's Hospital
Ann Arbor
Michigan
48109
United States
University of Minnesota/Masonic Cancer Center
Minneapolis
Minnesota
55455
United States
University of Mississippi Medical Center
Jackson
Mississippi
39216
United States
Children's Mercy Hospital and Clinics
Kansas City
Missouri
64108
United States
Alliance for Childhood Diseases
Las Vegas
Nevada
89135
United States
Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Morristown Medical Center
Morristown
New Jersey
07960
United States
Rutgers cancer Institute of NJ
New Brunswick
New Jersey
08901
United States
Cohen Children's Medical Center
New Hyde Park
New York
11040
United States
Columbia University/Herbert Irving Cancer Center
New York
New York
10032
United States
Memorial Sloan Kettering Cancer Center
New York
New York
10065
United States
New York Medical College
Valhalla
New York
10595
United States
Cincinnati Children's Hospital Medical Center
Cincinnati
Ohio
45229
United States
Nationwide Children's Hospital
Columbus
Ohio
43205
United States
University of Oklahoma Health Sciences Center
Oklahoma City
Oklahoma
73104
United States
Oregon Health & Science University
Portland
Oregon
97239
United States
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
19104
United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh
Pennsylvania
15224
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37232
United States
Dell Children's Medical Center of Central Texas
Austin
Texas
78723
United States
The University of Texas Southwestern Medical Center
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
FG002
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
FG003
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
FG004
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory high grade glioma (HGG) received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
FG0005 subjects
FG00118 subjects
FG00210 subjects
FG00320 subjects
FG00411 subjects
COMPLETED
FG0000 subjects
FG0013 subjects
FG0021 subjects
FG0032 subjects
FG0043 subjects
NOT COMPLETED
FG0005 subjects
FG00115 subjects
FG0029 subjects
FG00318 subjects
FG0048 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG0041 subjects
Death
FG0003 subjects
FG00114 subjects
FG0029 subjects
FG00316 subjects
FG004
Sponsor's decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Safety Analysis Set (SAS) included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
BG002
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
BG003
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
BG004
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0005
BG00118
BG00210
BG00320
BG00411
BG00564
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
2-11 years
Title
Measurements
BG0000
BG00116
BG0023
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG00110
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0017
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0011
BG002
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
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus
MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. DLT was graded according to common terminology criteria for adverse events (CTCAE) version 4.03.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Participants with recurrent or refractory solid tumors received lenvatinib 8 or 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG00023
Title
Denominators
Categories
Title
Measurements
OG00011
Primary
Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus
The RP2D of lenvatinib in combination with everolimus was determined by Dose Escalation Committee (DEC) based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v4.03.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Participants with recurrent or refractory solid tumors received lenvatinib 8 or 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG000
Primary
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Posted
Count of Participants
Participants
From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Primary
Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Posted
Count of Participants
Participants
From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Primary
Phase 2: Objective Response Rate (ORR) at Week 16
ORR at Week 16 was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at Week 16 based on investigator assessment according to response evaluation criteria in solid tumors (RECIST) version 1.1 for non-HGG cohorts and response assessment in neuro-oncology (RANO) for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.
Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.
Posted
Number
95% Confidence Interval
percentage of participants
Week 16
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Secondary
Phase 1: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.
Posted
Number
95% Confidence Interval
percentage of participants
From the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 16.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
ORR was defined as the percentage of participants with BOR of CR or PR based on investigator assessment according to RECIST version 1.1 for non-HGG cohorts and RANO for HGG cohort. CR was defined as disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.
Posted
Number
95% Confidence Interval
percentage of participants
From the date of the first dose of study drug to the date of first documentation of disease progression or death, which ever occurred first (up to 6.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Secondary
Phase 1: Disease Control Rate (DCR)
DCR was defined as percentage of participants with a confirmed CR, PR, or stable disease (SD) (SD duration >=7 weeks since the first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Posted
Number
95% Confidence Interval
percentage of participants
From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 2: Disease Control Rate (DCR)
DCR was defined as percentage of participants with confirmed CR, PR, or SD (SD duration greater than or equal to [>=] 7 weeks since first dose of study treatment) divided by number of participants in analysis set. DCR was assessed by investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to progressive disease.
Posted
Number
95% Confidence Interval
percentage of participants
From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Secondary
Phase 1: Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG participants or RANO for HGG participants. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Posted
Number
95% Confidence Interval
percentage of participants
From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 2: Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants who had BOR of CR, PR, or durable SD (SD duration >=23 weeks since the first dose of study treatment) divided by number of participants in analysis set. CBR was assessed by an investigator based on RECIST v1.1 for non-HGG cohorts or RANO for HGG cohort. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to the first efficacy assessment due to PD.
Posted
Number
95% Confidence Interval
percentage of participants
From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Secondary
Phase 1: Duration of Response (DOR)
DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohorts, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus). Here, 'overall number of participants analyzed' signifies participants who had CR or PR (0 participants hence, none were analyzed for this outcome measure).
Posted
From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 16.5 months)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 2: Duration of Response (DOR)
DOR was defined as the time (in months) from the date of first observation of confirmed response (PR or CR) to the date of the first observation of progression based on the investigator's assessment utilizing RECIST 1.1 for non-HGG cohorts and RANO for HGG cohort, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Evaluable analysis set included all evaluable participants who have measurable disease present at baseline, and at least one postbaseline efficacy assessment, unless they have discontinued prior to first efficacy assessment due to progressive disease. Here, 'overall number of participants analyzed' signifies participants who had CR or PR.
Posted
Median
95% Confidence Interval
months
From date of the first observation of CR or PR until the date of first observation of progression or date of death (up to 6.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Secondary
Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])
AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.
Posted
Mean
Standard Deviation
nanogram*hour per milliliter (ng*hr/mL)
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)
Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.
Posted
Mean
Standard Deviation
nanogram per milliliter (ng/mL)
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)
Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.
Posted
Median
Full Range
hours
Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib
Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.
Pharmacokinetic analysis set included participants who had at least one measurable postdose plasma concentration with an adequately documented drug administration history. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure and 'number analyzed' signifies participants who were evaluable for given timepoints of this outcome measure. Pharmacokinetic data was planned to be analyzed for Phase 1 only.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Secondary
Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event is continuous. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Posted
Count of Participants
Participants
From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Secondary
Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
A TESAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An adverse event was defined as any untoward medical occurrence in a participant administered an investigational product.
SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).
Posted
Count of Participants
Participants
From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)
ID
Title
Description
OG000
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Time Frame
From date of first dose up to 28 days after the last dose of study treatment (Phase 1: Up to 17.5 months; Phase 2: Up to 7.5 months)
Description
SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Participants with recurrent or refractory solid tumors received lenvatinib 8 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
14
18
12
18
18
18
EG002
Phase 2: Cohort 1, Ewing Sarcoma
Participants with recurrent or refractory ewing sarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
9
10
6
10
10
10
EG003
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
17
20
8
20
19
20
EG004
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
8
11
8
11
11
11
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG0031 events1 affected20 at risk
EG0040 events0 affected11 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pain
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Face oedema
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pyrexia
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0023 events3 affected10 at risk
EG003
Pneumonia aspiration
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Sepsis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Upper respiratory tract infections
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tendon rupture
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Malignant pleural effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Headache
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Nystagmus
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Seizure
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events3 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events3 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypotension
Vascular disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Eyelid oedema
Eye disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Mouth haemorrhage
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Oral cavity fistula
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pneumatosis intestinalis
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Cerebrospinal fluid leakage
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Depressed level of consciousness
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Encephalopathy
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hydrocephalus
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Optic neuritis
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Haemothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 25.1
Systematic Assessment
EG0006 events2 affected5 at risk
EG00116 events6 affected18 at risk
EG00217 events5 affected10 at risk
EG00310 events7 affected20 at risk
EG0045 events1 affected11 at risk
Sinus bradycardia
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0006 events2 affected5 at risk
EG0015 events4 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Wolff-Parkinson-White syndrome
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 25.1
Systematic Assessment
EG0003 events2 affected5 at risk
EG00113 events10 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Hyperparathyroidism
Endocrine disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dry eye
Eye disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Miosis
Eye disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Eye pain
Eye disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Vision blurred
Eye disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0003 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0004 events3 affected5 at risk
EG00116 events9 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Anal incontinence
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0004 events2 affected5 at risk
EG0014 events3 affected18 at risk
EG0025 events4 affected10 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG00010 events3 affected5 at risk
EG00123 events10 affected18 at risk
EG00210 events5 affected10 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Mouth haemorrhage
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0009 events4 affected5 at risk
EG0018 events5 affected18 at risk
EG0024 events3 affected10 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG00010 events4 affected5 at risk
EG0018 events5 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG00010 events3 affected5 at risk
EG00120 events11 affected18 at risk
EG0027 events3 affected10 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0023 events1 affected10 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Fatigue
General disorders
MedDRA 25.1
Systematic Assessment
EG0004 events3 affected5 at risk
EG0019 events6 affected18 at risk
EG0027 events6 affected10 at risk
EG003
Influenza like illness
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Localised oedema
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Pyrexia
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0017 events5 affected18 at risk
EG0028 events4 affected10 at risk
EG003
Pain
General disorders
MedDRA 25.1
Systematic Assessment
EG0007 events3 affected5 at risk
EG0012 events2 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Oedema peripheral
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Malaise
General disorders
MedDRA 25.1
Systematic Assessment
EG0002 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0017 events3 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Peripheral swelling
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Asthenia
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Face oedema
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Gait disturbances
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Steatohepatitis
Hepatobiliary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Contrast media allergy
Immune system disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Device related infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Otitis media
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0003 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Skin infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Upper respiratory tract infections
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0002 events2 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Otitis media acute
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Rash pustular
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Allergic transfusion reaction
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Stoma site pain
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tendon rupture
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Wrist fracture
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Wound complication
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Wound dehiscence
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG00110 events5 affected18 at risk
EG0027 events3 affected10 at risk
EG003
Amylase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG00113 events5 affected18 at risk
EG0026 events4 affected10 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Blood cholesterol increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG00123 events6 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Blood thyroid stimulating hormone increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Blood fibrinogen decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 25.1
Systematic Assessment
EG0002 events2 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Haemoglobin increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0014 events3 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Lipase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG00014 events3 affected5 at risk
EG00113 events6 affected18 at risk
EG00227 events8 affected10 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0006 events3 affected5 at risk
EG00112 events4 affected18 at risk
EG0027 events3 affected10 at risk
EG003
Platelet count decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0006 events2 affected5 at risk
EG00122 events7 affected18 at risk
EG0029 events5 affected10 at risk
EG003
Platelet count increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Weight decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0003 events2 affected5 at risk
EG00112 events6 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Weight increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 25.1
Systematic Assessment
EG0007 events2 affected5 at risk
EG00116 events6 affected18 at risk
EG00217 events6 affected10 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0007 events4 affected5 at risk
EG0015 events4 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0002 events2 affected5 at risk
EG0015 events2 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0015 events4 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypermagnesaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0024 events2 affected10 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0003 events2 affected5 at risk
EG00151 events11 affected18 at risk
EG00218 events5 affected10 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0019 events4 affected18 at risk
EG00213 events5 affected10 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0014 events4 affected18 at risk
EG0027 events5 affected10 at risk
EG003
Hypocholesterolaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0012 events2 affected18 at risk
EG0026 events4 affected10 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0017 events6 affected18 at risk
EG00215 events7 affected10 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0016 events3 affected18 at risk
EG00214 events8 affected10 at risk
EG003
Hypernatraemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0003 events1 affected5 at risk
EG0013 events2 affected18 at risk
EG0025 events3 affected10 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0004 events4 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0012 events2 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0004 events3 affected5 at risk
EG0015 events2 affected18 at risk
EG0025 events1 affected10 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0019 events4 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Joint range of motion decreased
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0013 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Myositis
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0014 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Periostitis
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pain in jaw
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Fibrous cortical defect
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Ataxia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Headache
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG00014 events3 affected5 at risk
EG00110 events8 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hydrocephalus
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypersomnia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Seizure
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Tremor
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Intracranial haematoma
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0002 events1 affected5 at risk
EG0013 events2 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Depression
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0003 events2 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Agitation
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Irritability
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Restlessness
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0004 events1 affected5 at risk
EG00137 events8 affected18 at risk
EG00215 events8 affected10 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0012 events2 affected18 at risk
EG0025 events4 affected10 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Micturition urgency
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0002 events2 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0002 events1 affected5 at risk
EG0013 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Urinary tract pain
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Glycosuria
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0022 events1 affected10 at risk
EG003
Renal tubular dysfunction
Renal and urinary disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA 25.1
Systematic Assessment
EG0002 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0017 events4 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0014 events2 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0002 events2 affected5 at risk
EG0013 events2 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0014 events4 affected18 at risk
EG0023 events2 affected10 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events2 affected18 at risk
EG0025 events2 affected10 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Tachypnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0014 events3 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0016 events4 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected18 at risk
EG0022 events2 affected10 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0016 events2 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Scab
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Skin atrophy
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Hot flush
Vascular disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Hypertension
Vascular disorders
MedDRA 25.1
Systematic Assessment
EG00014 events4 affected5 at risk
EG00119 events13 affected18 at risk
EG0024 events3 affected10 at risk
EG003
Hypotension
Vascular disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected10 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected5 at risk
EG0013 events3 affected18 at risk
EG0020 events0 affected10 at risk
EG003
Malignant pleural effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Units
Counts
Participants
OG00010
OG00120
OG00210
Title
Denominators
Categories
Title
Measurements
OG0000.0± 0.0(0.0 to 30.8)
OG00110.0± 1.2(1.2 to 31.7)
OG0020± 0.0(0.0 to 30.8)
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG0003
OG00115
Title
Denominators
Categories
Title
Measurements
OG0000.0± 0.0(0.0 to 70.8)
OG0010.0± 0.0(0.0 to 21.8)
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG0005
OG00118
Title
Denominators
Categories
Title
Measurements
OG00020.0± 0.5(0.5 to 71.6)
OG00150.0± 26.0(26.0 to 74.0)
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG0005
OG00118
Title
Denominators
Categories
Title
Measurements
OG00020.0± 0.5(0.5 to 71.6)
OG00122.2± 6.4(6.4 to 47.6)
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Participants with recurrent or refractory solid tumors received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily in cycle 1 (each cycle was 28 days) until the occurrence of PD, clinical benefit, development of unacceptable toxicity leading to withdrawal from the study, study discontinuation or for a maximum of 18 cycles (each cycle was 28 days) whichever occurred first.
Units
Counts
Participants
OG0000
OG0010
OG001
Phase 2: Cohort 2, Rhabdomyosarcoma
Participants with recurrent or refractory rhabdomyosarcoma received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Units
Counts
Participants
OG0000
OG0012
OG0020
Title
Denominators
Categories
Title
Measurements
OG0012.4(2.1 to NA)Upper limit of 95% Confidence Interval could not be estimated as insufficient number of participants were available for analysis.
Units
Counts
Participants
OG0005
OG00118
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0005
ParticipantsOG00118
Title
Measurements
OG0002338.0± 1633.41
OG0013281.1± 1064.72
Cycle 1 Day 15
ParticipantsOG0005
ParticipantsOG00117
Title
Measurements
OG0001328.0± 520.69
OG001
Units
Counts
Participants
OG0005
OG00118
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0005
ParticipantsOG00118
Title
Measurements
OG000240.20± 130.892
OG001404.13± 121.473
Cycle 1 Day 15
ParticipantsOG0005
ParticipantsOG00117
Title
Measurements
OG000314.20± 149.527
OG001
Units
Counts
Participants
OG0005
OG00118
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0005
ParticipantsOG00118
Title
Measurements
OG0003.000(2.000 to 4.000)
OG0012.890(1.000 to 7.78)
Cycle 1 Day 15
ParticipantsOG0005
ParticipantsOG00117
Title
Measurements
OG0003.950(2.000 to 8.05)
OG001
Units
Counts
Participants
OG0005
OG00117
Title
Denominators
Categories
Cycle 1 Day 1: Pre-dose
ParticipantsOG0005
ParticipantsOG00117
Title
Measurements
OG0000.0± 0.0
OG0010.0± 0.00
Cycle 1 Day 2: Pre-dose
ParticipantsOG0005
ParticipantsOG00117
Title
Measurements
OG0002.1± 1.34
OG001
Cycle 1 Day 15: Pre-dose
ParticipantsOG0005
ParticipantsOG00115
Title
Measurements
OG0003.2± 2.42
OG001
Cycle 1 Day 22: Pre-dose
ParticipantsOG0005
ParticipantsOG00115
Title
Measurements
OG0002.8± 1.96
OG001
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.
Units
Counts
Participants
OG00010
OG00120
OG00211
Title
Denominators
Categories
Title
Measurements
OG00010
OG00119
OG00211
OG002
Phase 2: Cohort 3, HGG
Participants with recurrent or refractory HGG received lenvatinib 11 mg/m^2, capsules, orally, once daily in combination with everolimus 3 mg/m^2, tablets, orally, once daily for up to 7 cycles (each cycle was 28 days) unless participant discontinued early from the study.