Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors

• ClinicalTrials.gov Identifier: NCT03245151
• Recruitment Status: Completed
• First Posted: August 10, 2017
• Results First Posted: August 30, 2023
• Last Update Posted: August 30, 2023
• Sponsor: Eisai Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Eisai Inc.

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent and Refractory Solid Tumors
• Interventions: Drug: Lenvatinib; Drug: Everolimus
• Enrollment: 64

Participant Flow

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.
Pre-assignment Details	A total of 86 participants were screened, out of which 64 were enrolled and 9 participants completed the study.

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description	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.	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.	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.	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.	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.
Period Title: Overall Study
Started	5	18	10	20	11
Completed	0	3	1	2	3
Not Completed	5	15	9	18	8
Reason Not Completed
Withdrawal by Subject	2	0	0	2	1
Death	3	14	9	16	7
Sponsor's decision	0	1	0	0	0

Baseline Characteristics

Arm/Group Title		Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG	Total
Arm/Group Description		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.	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.	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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		5	18	10	20	11	64
Baseline Analysis Population Description		Safety Analysis Set (SAS) included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	5 participants	18 participants	10 participants	20 participants	11 participants	64 participants
2-11 years		0 0.0%	16 88.9%	3 30.0%	9 45.0%	3 27.3%	31 48.4%
12-17 years		4 80.0%	1 5.6%	3 30.0%	6 30.0%	7 63.6%	21 32.8%
18-64 years		1 20.0%	1 5.6%	4 40.0%	5 25.0%	1 9.1%	12 18.8%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	18 participants	10 participants	20 participants	11 participants	64 participants
	Female	2 40.0%	10 55.6%	3 30.0%	8 40.0%	8 72.7%	31 48.4%
	Male	3 60.0%	8 44.4%	7 70.0%	12 60.0%	3 27.3%	33 51.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	18 participants	10 participants	20 participants	11 participants	64 participants
	Hispanic or Latino	1 20.0%	7 38.9%	2 20.0%	2 10.0%	0 0.0%	12 18.8%
	Not Hispanic or Latino	4 80.0%	11 61.1%	8 80.0%	18 90.0%	11 100.0%	52 81.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	18 participants	10 participants	20 participants	11 participants	64 participants
	American Indian or Alaska Native	0 0.0%	1 5.6%	0 0.0%	0 0.0%	0 0.0%	1 1.6%
	Asian	0 0.0%	1 5.6%	1 10.0%	0 0.0%	0 0.0%	2 3.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 20.0%	1 5.6%	0 0.0%	1 5.0%	3 27.3%	6 9.4%
	White	3 60.0%	11 61.1%	9 90.0%	16 80.0%	6 54.5%	45 70.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 20.0%	4 22.2%	0 0.0%	3 15.0%	2 18.2%	10 15.6%

Outcome Measures

1. Primary Outcome

Title	Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib in Combination With Everolimus
Description	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.
Time Frame	Cycle 1 (Each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 1: Lenvatinib + Everolimus (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	23
Measure Type: Number; Unit of Measure: milligram per square meter (mg/m^2)
	11

2. Primary Outcome

Title	Phase 1: Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Everolimus
Description	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.
Time Frame	Cycle 1 (Each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 1: Lenvatinib + Everolimus (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	23
Measure Type: Number; Unit of Measure: mg/m^2
	11

3. Primary Outcome

Title	Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Description	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.
Time Frame	From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5	18
Measure Type: Count of Participants; Unit of Measure: Participants
	5 100.0%	18 100.0%

4. Primary Outcome

Title	Phase 1: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
Description	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.
Time Frame	From date of first dose up to 28 days after the last dose of study treatment (Up to 17.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5	18
Measure Type: Count of Participants; Unit of Measure: Participants
	2 40.0%	12 66.7%

5. Primary Outcome

Title	Phase 2: Objective Response Rate (ORR) at Week 16
Description	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.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	10
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0.0; (0.0 to 30.8)	10.0; (1.2 to 31.7)	0; (0.0 to 30.8)

6. Secondary Outcome

Title	Phase 1: Objective Response Rate (ORR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	3	15
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0.0; (0.0 to 70.8)	0.0; (0.0 to 21.8)

7. Secondary Outcome

Title	Phase 2: Objective Response Rate (ORR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	10
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0.0; (0.0 to 30.8)	10.0; (1.2 to 31.7)	0.0; (0.0 to 30.8)

8. Secondary Outcome

Title	Phase 1: Disease Control Rate (DCR)
Description	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.
Time Frame	From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.0; (0.5 to 71.6)	50.0; (26.0 to 74.0)

9. Secondary Outcome

Title	Phase 2: Disease Control Rate (DCR)
Description	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.
Time Frame	From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	10
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	40.0; (12.2 to 73.8)	40.0; (19.1 to 63.9)	30.0; (6.7 to 65.2)

10. Secondary Outcome

Title	Phase 1: Clinical Benefit Rate (CBR)
Description	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.
Time Frame	From first dose of study drug until PD or death, whichever occurred first (up to 16.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.0; (0.5 to 71.6)	22.2; (6.4 to 47.6)

11. Secondary Outcome

Title	Phase 2: Clinical Benefit Rate (CBR)
Description	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.
Time Frame	From first dose of study drug until PD or death, whichever occurred first (up to 6.5 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	10
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.0; (2.5 to 55.6)	10.0; (1.2 to 31.7)	0.0; (0.0 to 30.8)

12. Secondary Outcome

Title	Phase 1: Duration of Response (DOR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:	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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

13. Secondary Outcome

Title	Phase 2: Duration of Response (DOR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	0	2	0
Median (95% Confidence Interval); Unit of Measure: months
		2.4 [1]; (2.1 to NA)

[1]

Upper limit of 95% Confidence Interval could not be estimated as insufficient number of participants were available for analysis.

14. Secondary Outcome

Title	Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Lenvatinib (AUC[0-t Hours])
Description	AUC0-t of lenvatinib was quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
Time Frame	Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:		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.
Overall Number of Participants Analyzed		5	18
Mean (Standard Deviation); Unit of Measure: nanogram*hour per milliliter (ng*hr/mL)
Cycle 1 Day 1	Number Analyzed	5 participants	18 participants
		2338.0 (1633.41)	3281.1 (1064.72)
Cycle 1 Day 15	Number Analyzed	5 participants	17 participants
		1328.0 (520.69)	2139.8 (1156.48)

15. Secondary Outcome

Title	Phase 1: Maximum Plasma Concentration of Lenvatinib (Cmax)
Description	Cmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Time Frame	Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:		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.
Overall Number of Participants Analyzed		5	18
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter (ng/mL)
Cycle 1 Day 1	Number Analyzed	5 participants	18 participants
		240.20 (130.892)	404.13 (121.473)
Cycle 1 Day 15	Number Analyzed	5 participants	17 participants
		314.20 (149.527)	447.62 (272.790)

16. Secondary Outcome

Title	Phase 1: Time to Reach Maximum Plasma Concentration (Cmax) of Lenvatinib (Tmax)
Description	Tmax of lenvatinib was quantified using validated liquid LC-MS/MS methods.
Time Frame	Cycle 1 Days 1 and 15: 0-8 hours post-dose (Cycle length=28 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:		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.
Overall Number of Participants Analyzed		5	18
Median (Full Range); Unit of Measure: hours
Cycle 1 Day 1	Number Analyzed	5 participants	18 participants
		3.000; (2.000 to 4.000)	2.890; (1.000 to 7.78)
Cycle 1 Day 15	Number Analyzed	5 participants	17 participants
		3.950; (2.000 to 8.05)	2.950; (0 to 8.02)

17. Secondary Outcome

Title	Phase 1: Trough Concentrations (Ctrough) of Everolimus When Administered in Combination With Lenvatinib
Description	Trough concentrations of everolimus was quantified using validated liquid LC-MS/MS methods.
Time Frame	Cycle 1 Days 1, 2, 15 and 22: Pre-dose (Cycle length=28 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2	Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2
Arm/Group Description:		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.
Overall Number of Participants Analyzed		5	17
Mean (Standard Deviation); Unit of Measure: ng/mL
Cycle 1 Day 1: Pre-dose	Number Analyzed	5 participants	17 participants
		0.0 (0.0)	0.0 (0.00)
Cycle 1 Day 2: Pre-dose	Number Analyzed	5 participants	17 participants
		2.1 (1.34)	2.2 (1.13)
Cycle 1 Day 15: Pre-dose	Number Analyzed	5 participants	15 participants
		3.2 (2.42)	5.1 (2.98)
Cycle 1 Day 22: Pre-dose	Number Analyzed	5 participants	15 participants
		2.8 (1.96)	4.2 (2.73)

18. Secondary Outcome

Title	Phase 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Description	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.
Time Frame	From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	11
Measure Type: Count of Participants; Unit of Measure: Participants
	10 100.0%	19 95.0%	11 100.0%

19. Secondary Outcome

Title	Phase 2: Number of Participants With Any Treatment-emergent Serious Adverse Event (TESAE)
Description	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.
Time Frame	From date of first dose up to 28 days after the last dose of study treatment (up to 7.5 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of study drug (Lenvatinib or Everolimus).

Arm/Group Title	Phase 2: Cohort 1, Ewing Sarcoma	Phase 2: Cohort 2, Rhabdomyosarcoma	Phase 2: Cohort 3, HGG
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	10	20	11
Measure Type: Count of Participants; Unit of Measure: Participants
	6 60.0%	8 40.0%	8 72.7%

Adverse Events

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)
Adverse Event Reporting Description	SAS included all participants who received at least 1 dose of study drug (lenvatinib or everolimus).
Arm/Group Title	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2		Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2		Phase 2: Cohort 1, Ewing Sarcoma		Phase 2: Cohort 2, Rhabdomyosarcoma		Phase 2: Cohort 3, HGG
Arm/Group Description	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.		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.		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.		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.
All-Cause Mortality
	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2		Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2		Phase 2: Cohort 1, Ewing Sarcoma		Phase 2: Cohort 2, Rhabdomyosarcoma		Phase 2: Cohort 3, HGG
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	4/5 (80.00%)		14/18 (77.78%)		9/10 (90.00%)		17/20 (85.00%)		8/11 (72.73%)
Serious Adverse Events
	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2		Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2		Phase 2: Cohort 1, Ewing Sarcoma		Phase 2: Cohort 2, Rhabdomyosarcoma		Phase 2: Cohort 3, HGG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40.00%)		12/18 (66.67%)		6/10 (60.00%)		8/20 (40.00%)		8/11 (72.73%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Eye disorders
Eyelid oedema † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Dysphagia † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Nausea † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Vomiting † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Diarrhoea † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Mouth haemorrhage † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Oral cavity fistula † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Pancreatitis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Pneumatosis intestinalis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
General disorders
Pain † 1	1/5 (20.00%)	1	2/18 (11.11%)	2	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Face oedema † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Pyrexia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	3/10 (30.00%)	3	1/20 (5.00%)	1	0/11 (0.00%)	0
Infections and infestations
Pneumonia aspiration † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Sepsis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Upper respiratory tract infections † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Pneumonia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Injury, poisoning and procedural complications
Tendon rupture † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Aspartate aminotransferase increased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Hypophosphataemia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Musculoskeletal pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Muscular weakness † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Musculoskeletal chest pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Myalgia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Tumour haemorrhage † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Cancer pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Nervous system disorders
Dysarthria † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Headache † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Nystagmus † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Seizure † 1	0/5 (0.00%)	0	3/18 (16.67%)	3	0/10 (0.00%)	0	0/20 (0.00%)	0	2/11 (18.18%)	2
Cerebrospinal fluid leakage † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Depressed level of consciousness † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Encephalopathy † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Hydrocephalus † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Optic neuritis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Paraesthesia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Psychiatric disorders
Mental status changes † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	0/5 (0.00%)	0	3/18 (16.67%)	3	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Pneumothorax † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	1/20 (5.00%)	1	0/11 (0.00%)	0
Respiratory failure † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Cough † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Haemothorax † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Pleural effusion † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	2/10 (20.00%)	2	1/20 (5.00%)	1	0/11 (0.00%)	0
Vascular disorders
Hypotension † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Deep vein thrombosis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Phase 1: Lenvatinib 8 mg/m^2 + Everolimus 3 mg/m^2		Phase 1: Lenvatinib 11 mg/m^2 + Everolimus 3 mg/m^2		Phase 2: Cohort 1, Ewing Sarcoma		Phase 2: Cohort 2, Rhabdomyosarcoma		Phase 2: Cohort 3, HGG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100.00%)		18/18 (100.00%)		10/10 (100.00%)		19/20 (95.00%)		11/11 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/5 (40.00%)	6	6/18 (33.33%)	16	5/10 (50.00%)	17	7/20 (35.00%)	10	1/11 (9.09%)	5
Lymphopenia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Neutropenia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Cardiac disorders
Sinus bradycardia † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	3/20 (15.00%)	3	0/11 (0.00%)	0
Bradycardia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Sinus tachycardia † 1	2/5 (40.00%)	6	4/18 (22.22%)	5	1/10 (10.00%)	2	3/20 (15.00%)	5	0/11 (0.00%)	0
Tachycardia † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Wolff-Parkinson-White syndrome † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Ear and labyrinth disorders
Ear pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Endocrine disorders
Hyperthyroidism † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	1/20 (5.00%)	1	1/11 (9.09%)	1
Hypothyroidism † 1	2/5 (40.00%)	3	10/18 (55.56%)	13	2/10 (20.00%)	3	8/20 (40.00%)	14	6/11 (54.55%)	7
Hyperparathyroidism † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Eye disorders
Dry eye † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Miosis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Eye pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Vision blurred † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	1/11 (9.09%)	1
Gastrointestinal disorders
Abdominal distension † 1	1/5 (20.00%)	3	1/18 (5.56%)	1	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Abdominal pain † 1	3/5 (60.00%)	4	9/18 (50.00%)	16	1/10 (10.00%)	1	7/20 (35.00%)	10	4/11 (36.36%)	5
Abdominal pain upper † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	2	1/20 (5.00%)	1	1/11 (9.09%)	1
Anal incontinence † 1	0/5 (0.00%)	0	1/18 (5.56%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Aphthous ulcer † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Cheilitis † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Constipation † 1	2/5 (40.00%)	4	3/18 (16.67%)	4	4/10 (40.00%)	5	6/20 (30.00%)	8	3/11 (27.27%)	3
Diarrhoea † 1	3/5 (60.00%)	10	10/18 (55.56%)	23	5/10 (50.00%)	10	8/20 (40.00%)	11	7/11 (63.64%)	9
Dry mouth † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Dysphagia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	2/20 (10.00%)	2	1/11 (9.09%)	1
Gingival pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Mouth haemorrhage † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Nausea † 1	4/5 (80.00%)	9	5/18 (27.78%)	8	3/10 (30.00%)	4	9/20 (45.00%)	14	4/11 (36.36%)	5
Oral pain † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	0/11 (0.00%)	0
Stomatitis † 1	4/5 (80.00%)	10	5/18 (27.78%)	8	2/10 (20.00%)	2	9/20 (45.00%)	21	2/11 (18.18%)	3
Toothache † 1	0/5 (0.00%)	0	1/18 (5.56%)	3	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Vomiting † 1	3/5 (60.00%)	10	11/18 (61.11%)	20	3/10 (30.00%)	7	7/20 (35.00%)	11	7/11 (63.64%)	10
Pancreatitis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	3	1/20 (5.00%)	1	0/11 (0.00%)	0
Flatulence † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
General disorders
Fatigue † 1	3/5 (60.00%)	4	6/18 (33.33%)	9	6/10 (60.00%)	7	11/20 (55.00%)	16	3/11 (27.27%)	5
Influenza like illness † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Localised oedema † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Pyrexia † 1	1/5 (20.00%)	1	5/18 (27.78%)	7	4/10 (40.00%)	8	3/20 (15.00%)	4	0/11 (0.00%)	0
Pain † 1	3/5 (60.00%)	7	2/18 (11.11%)	2	1/10 (10.00%)	2	1/20 (5.00%)	1	1/11 (9.09%)	1
Oedema peripheral † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	1/10 (10.00%)	1	2/20 (10.00%)	2	1/11 (9.09%)	1
Malaise † 1	1/5 (20.00%)	2	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Non-cardiac chest pain † 1	0/5 (0.00%)	0	3/18 (16.67%)	7	1/10 (10.00%)	1	5/20 (25.00%)	8	1/11 (9.09%)	1
Peripheral swelling † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Asthenia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Face oedema † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Gait disturbances † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	1/11 (9.09%)	1
Hepatobiliary disorders
Hypertransaminasaemia † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Steatohepatitis † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Immune system disorders
Contrast media allergy † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Infections and infestations
Conjunctivitis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Device related infection † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Oral candidiasis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Otitis media † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Pharyngitis † 1	1/5 (20.00%)	3	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Sinusitis † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Skin infection † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Upper respiratory tract infections † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Urinary tract infection † 1	2/5 (40.00%)	2	1/18 (5.56%)	1	0/10 (0.00%)	0	3/20 (15.00%)	3	0/11 (0.00%)	0
Vulvovaginal mycotic infection † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Otitis media acute † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Rash pustular † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	1/11 (9.09%)	2
Respiratory tract infection viral † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Pneumonia † 1	0/5 (0.00%)	0	3/18 (16.67%)	3	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Injury, poisoning and procedural complications
Allergic transfusion reaction † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Contusion † 1	0/5 (0.00%)	0	1/18 (5.56%)	3	0/10 (0.00%)	0	1/20 (5.00%)	1	1/11 (9.09%)	1
Fall † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	2
Stoma site pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Tendon rupture † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Wrist fracture † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Procedural pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Wound complication † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Wound dehiscence † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Investigations
Alanine aminotransferase increased † 1	0/5 (0.00%)	0	5/18 (27.78%)	10	3/10 (30.00%)	7	7/20 (35.00%)	7	3/11 (27.27%)	4
Amylase increased † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Aspartate aminotransferase increased † 1	0/5 (0.00%)	0	5/18 (27.78%)	13	4/10 (40.00%)	6	8/20 (40.00%)	13	4/11 (36.36%)	5
Blood alkaline phosphatase increased † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	1/10 (10.00%)	1	1/20 (5.00%)	1	1/11 (9.09%)	3
Blood cholesterol increased † 1	1/5 (20.00%)	1	6/18 (33.33%)	23	2/10 (20.00%)	2	11/20 (55.00%)	14	4/11 (36.36%)	12
Blood creatinine increased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	2	2/20 (10.00%)	4	0/11 (0.00%)	0
Blood thyroid stimulating hormone increased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	2	2/20 (10.00%)	3	0/11 (0.00%)	0
Blood fibrinogen decreased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Blood lactate dehydrogenase increased † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	2/10 (20.00%)	3	2/20 (10.00%)	2	0/11 (0.00%)	0
Ejection fraction decreased † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	1/11 (9.09%)	1
Electrocardiogram QT prolonged † 1	2/5 (40.00%)	2	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Haemoglobin increased † 1	0/5 (0.00%)	0	3/18 (16.67%)	4	1/10 (10.00%)	1	3/20 (15.00%)	9	3/11 (27.27%)	5
Gamma-glutamyltransferase increased † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
International normalised ratio increased † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Lipase increased † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	4/20 (20.00%)	6	1/11 (9.09%)	1
Lymphocyte count decreased † 1	3/5 (60.00%)	14	6/18 (33.33%)	13	8/10 (80.00%)	27	11/20 (55.00%)	32	2/11 (18.18%)	10
Neutrophil count decreased † 1	3/5 (60.00%)	6	4/18 (22.22%)	12	3/10 (30.00%)	7	7/20 (35.00%)	14	2/11 (18.18%)	9
Platelet count decreased † 1	2/5 (40.00%)	6	7/18 (38.89%)	22	5/10 (50.00%)	9	10/20 (50.00%)	21	3/11 (27.27%)	4
Platelet count increased † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
SARS-CoV-2 test positive † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Weight decreased † 1	2/5 (40.00%)	3	6/18 (33.33%)	12	1/10 (10.00%)	2	6/20 (30.00%)	10	0/11 (0.00%)	0
Weight increased † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	3
White blood cell count decreased † 1	2/5 (40.00%)	7	6/18 (33.33%)	16	6/10 (60.00%)	17	8/20 (40.00%)	24	2/11 (18.18%)	8
Metabolism and nutrition disorders
Decreased appetite † 1	4/5 (80.00%)	7	4/18 (22.22%)	5	2/10 (20.00%)	3	6/20 (30.00%)	9	2/11 (18.18%)	2
Dehydration † 1	2/5 (40.00%)	2	2/18 (11.11%)	5	1/10 (10.00%)	2	4/20 (20.00%)	5	0/11 (0.00%)	0
Hyperglycaemia † 1	0/5 (0.00%)	0	4/18 (22.22%)	5	2/10 (20.00%)	2	4/20 (20.00%)	6	3/11 (27.27%)	7
Hypercalcaemia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Hypercholesterolaemia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Hyperkalaemia † 1	1/5 (20.00%)	1	2/18 (11.11%)	2	0/10 (0.00%)	0	4/20 (20.00%)	4	0/11 (0.00%)	0
Hypermagnesaemia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	2/10 (20.00%)	4	3/20 (15.00%)	6	0/11 (0.00%)	0
Hypertriglyceridaemia † 1	2/5 (40.00%)	3	11/18 (61.11%)	51	5/10 (50.00%)	18	12/20 (60.00%)	26	6/11 (54.55%)	22
Hypoalbuminaemia † 1	0/5 (0.00%)	0	4/18 (22.22%)	9	5/10 (50.00%)	13	4/20 (20.00%)	14	0/11 (0.00%)	0
Hypocalcaemia † 1	0/5 (0.00%)	0	4/18 (22.22%)	4	5/10 (50.00%)	7	4/20 (20.00%)	6	0/11 (0.00%)	0
Hypocholesterolaemia † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Hypokalaemia † 1	1/5 (20.00%)	1	2/18 (11.11%)	2	4/10 (40.00%)	6	2/20 (10.00%)	2	1/11 (9.09%)	2
Hypomagnesaemia † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	2	2/20 (10.00%)	3	0/11 (0.00%)	0
Hyponatraemia † 1	1/5 (20.00%)	1	6/18 (33.33%)	7	7/10 (70.00%)	15	2/20 (10.00%)	3	1/11 (9.09%)	1
Hypophosphataemia † 1	1/5 (20.00%)	1	3/18 (16.67%)	6	8/10 (80.00%)	14	6/20 (30.00%)	10	1/11 (9.09%)	1
Hypernatraemia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Hyperphosphataemia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Hypoglycaemia † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	2/20 (10.00%)	3	0/11 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/5 (20.00%)	3	2/18 (11.11%)	3	3/10 (30.00%)	5	6/20 (30.00%)	11	3/11 (27.27%)	5
Back pain † 1	4/5 (80.00%)	4	1/18 (5.56%)	1	1/10 (10.00%)	1	4/20 (20.00%)	6	2/11 (18.18%)	2
Muscular weakness † 1	1/5 (20.00%)	1	2/18 (11.11%)	2	1/10 (10.00%)	2	2/20 (10.00%)	2	0/11 (0.00%)	0
Myalgia † 1	3/5 (60.00%)	4	2/18 (11.11%)	5	1/10 (10.00%)	5	4/20 (20.00%)	6	2/11 (18.18%)	2
Neck pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	3/20 (15.00%)	5	0/11 (0.00%)	0
Pain in extremity † 1	1/5 (20.00%)	1	4/18 (22.22%)	9	2/10 (20.00%)	2	5/20 (25.00%)	7	2/11 (18.18%)	3
Bone pain † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Joint range of motion decreased † 1	1/5 (20.00%)	1	2/18 (11.11%)	3	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Muscle spasms † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Musculoskeletal pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Myositis † 1	0/5 (0.00%)	0	1/18 (5.56%)	4	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Periostitis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Pain in jaw † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Spinal pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibrous cortical defect † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Tumour haemorrhage † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Tumour pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Cancer pain † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	2/10 (20.00%)	3	1/20 (5.00%)	3	0/11 (0.00%)	0
Malignant pleural effusion † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	2/10 (20.00%)	2	0/20 (0.00%)	0	0/11 (0.00%)	0
Nervous system disorders
Ataxia † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Dizziness † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	1/10 (10.00%)	1	2/20 (10.00%)	2	1/11 (9.09%)	1
Dysarthria † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Dysgeusia † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	0/11 (0.00%)	0
Headache † 1	3/5 (60.00%)	14	8/18 (44.44%)	10	1/10 (10.00%)	1	5/20 (25.00%)	5	5/11 (45.45%)	7
Hydrocephalus † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Hypersomnia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Lethargy † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Seizure † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Somnolence † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Tremor † 1	0/5 (0.00%)	0	1/18 (5.56%)	2	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Intracranial haematoma † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Haemorrhage intracranial † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Product Issues
Device dislocation † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/5 (20.00%)	2	2/18 (11.11%)	3	2/10 (20.00%)	2	4/20 (20.00%)	4	1/11 (9.09%)	1
Depression † 1	2/5 (40.00%)	3	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Agitation † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	2/10 (20.00%)	3	2/20 (10.00%)	2	0/11 (0.00%)	0
Irritability † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Restlessness † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Insomnia † 1	2/5 (40.00%)	3	2/18 (11.11%)	4	1/10 (10.00%)	1	2/20 (10.00%)	2	1/11 (9.09%)	1
Renal and urinary disorders
Proteinuria † 1	1/5 (20.00%)	4	8/18 (44.44%)	37	8/10 (80.00%)	15	10/20 (50.00%)	23	4/11 (36.36%)	4
Haematuria † 1	1/5 (20.00%)	1	2/18 (11.11%)	2	4/10 (40.00%)	5	6/20 (30.00%)	6	3/11 (27.27%)	3
Dysuria † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Micturition urgency † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Pollakiuria † 1	2/5 (40.00%)	2	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Urinary incontinence † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Urinary retention † 1	1/5 (20.00%)	2	2/18 (11.11%)	3	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Urinary tract pain † 1	0/5 (0.00%)	0	1/18 (5.56%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Glycosuria † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	2	0/20 (0.00%)	0	0/11 (0.00%)	0
Renal tubular dysfunction † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Reproductive system and breast disorders
Pelvic pain † 1	1/5 (20.00%)	2	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Cough † 1	1/5 (20.00%)	1	4/18 (22.22%)	7	1/10 (10.00%)	1	4/20 (20.00%)	5	1/11 (9.09%)	1
Dysphonia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Dyspnoea † 1	0/5 (0.00%)	0	2/18 (11.11%)	4	2/10 (20.00%)	2	4/20 (20.00%)	5	0/11 (0.00%)	0
Epistaxis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	1/10 (10.00%)	1	6/20 (30.00%)	9	1/11 (9.09%)	1
Hiccups † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Hypoxia † 1	0/5 (0.00%)	0	2/18 (11.11%)	2	2/10 (20.00%)	3	1/20 (5.00%)	1	0/11 (0.00%)	0
Nasal congestion † 1	2/5 (40.00%)	2	2/18 (11.11%)	3	1/10 (10.00%)	1	5/20 (25.00%)	5	0/11 (0.00%)	0
Oropharyngeal pain † 1	1/5 (20.00%)	1	4/18 (22.22%)	4	2/10 (20.00%)	3	7/20 (35.00%)	12	1/11 (9.09%)	1
Pleural effusion † 1	0/5 (0.00%)	0	2/18 (11.11%)	3	2/10 (20.00%)	5	1/20 (5.00%)	1	0/11 (0.00%)	0
Pneumothorax † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Productive cough † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Rhinitis allergic † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Rhinorrhoea † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Tachypnoea † 1	0/5 (0.00%)	0	3/18 (16.67%)	4	1/10 (10.00%)	1	2/20 (10.00%)	4	0/11 (0.00%)	0
Pulmonary oedema † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Respiratory distress † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Dermatitis acneiform † 1	1/5 (20.00%)	1	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	0/11 (0.00%)	0
Dermatitis contact † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Dry skin † 1	1/5 (20.00%)	1	4/18 (22.22%)	6	0/10 (0.00%)	0	2/20 (10.00%)	2	1/11 (9.09%)	1
Hyperhidrosis † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Palmar-plantar erythrodysaesthesia syndrome † 1	1/5 (20.00%)	1	1/18 (5.56%)	1	2/10 (20.00%)	2	1/20 (5.00%)	5	2/11 (18.18%)	5
Pruritus † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	3/20 (15.00%)	4	0/11 (0.00%)	0
Rash maculo-papular † 1	0/5 (0.00%)	0	2/18 (11.11%)	6	0/10 (0.00%)	0	3/20 (15.00%)	4	0/11 (0.00%)	0
Scab † 1	0/5 (0.00%)	0	1/18 (5.56%)	2	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Skin atrophy † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	1
Skin ulcer † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/11 (9.09%)	4
Urticaria † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Petechiae † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	0/11 (0.00%)	0
Erythemas † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/11 (0.00%)	0
Pain of skin † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
Vascular disorders
Hot flush † 1	0/5 (0.00%)	0	1/18 (5.56%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/11 (0.00%)	0
Hypertension † 1	4/5 (80.00%)	14	13/18 (72.22%)	19	3/10 (30.00%)	4	10/20 (50.00%)	18	4/11 (36.36%)	5
Hypotension † 1	0/5 (0.00%)	0	0/18 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/11 (0.00%)	0
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Eisai Medical Information
• Organization: Eisai Inc.
• Phone: 1-888-274-2378
• EMail: esi_oncmedinfo@eisai.com

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT03245151
• Other Study ID Numbers: E7080-A001-216
• First Submitted: August 3, 2017
• First Posted: August 10, 2017
• Results First Submitted: August 7, 2023
• Results First Posted: August 30, 2023
• Last Update Posted: August 30, 2023