Trial Outcomes & Findings for CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma (NCT NCT05440786)

Last Updated: 2026-04-13

Results Overview

PFS was defined as the time from randomization until the first occurrence of documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, or death from any cause in absence of progressive disease, whichever came first. Progressive disease (PD) was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using Bayesian analysis and are reported as posterior mean along with its 80% credible interval.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months)

Results posted on

2026-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	Abemaciclib + Irinotecan +Temozolomide Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m² (milligrams per square meter), administered orally twice daily (BID) for less than (\<18) years or 100 mg administered orally BID for greater than or equal to (≥)18 years. * Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Overall Study STARTED	30	16
Overall Study Received at Least One Dose of Study Drug	30	15
Overall Study COMPLETED	15	8
Overall Study NOT COMPLETED	15	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Abemaciclib + Irinotecan +Temozolomide Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m² (milligrams per square meter), administered orally twice daily (BID) for less than (\<18) years or 100 mg administered orally BID for greater than or equal to (≥)18 years. * Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Overall Study Withdrawal by Parent or Guardian	1	1
Overall Study Withdrawal by Subject	0	1
Overall Study Randomized but Not Treated	0	1
Overall Study On study (ongoing)	14	5

Baseline Characteristics

CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Total n=46 Participants Total of all reporting groups
Age, Continuous	16.7 Years STANDARD_DEVIATION 6.7 • n=193 Participants	17.1 Years STANDARD_DEVIATION 6.8 • n=193 Participants	16.8 Years STANDARD_DEVIATION 6.6 • n=386 Participants
Sex: Female, Male Female	9 Participants n=193 Participants	4 Participants n=193 Participants	13 Participants n=386 Participants
Sex: Female, Male Male	21 Participants n=193 Participants	12 Participants n=193 Participants	33 Participants n=386 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=193 Participants	3 Participants n=193 Participants	8 Participants n=386 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=193 Participants	10 Participants n=193 Participants	30 Participants n=386 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=193 Participants	3 Participants n=193 Participants	8 Participants n=386 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Asian	7 Participants n=193 Participants	2 Participants n=193 Participants	9 Participants n=386 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Black or African American	0 Participants n=193 Participants	1 Participants n=193 Participants	1 Participants n=386 Participants
Race (NIH/OMB) White	18 Participants n=193 Participants	11 Participants n=193 Participants	29 Participants n=386 Participants
Race (NIH/OMB) More than one race	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=193 Participants	2 Participants n=193 Participants	7 Participants n=386 Participants
Region of Enrollment United States	3 Participants n=193 Participants	2 Participants n=193 Participants	5 Participants n=386 Participants
Region of Enrollment Japan	7 Participants n=193 Participants	2 Participants n=193 Participants	9 Participants n=386 Participants
Region of Enrollment Italy	5 Participants n=193 Participants	0 Participants n=193 Participants	5 Participants n=386 Participants
Region of Enrollment France	4 Participants n=193 Participants	3 Participants n=193 Participants	7 Participants n=386 Participants
Region of Enrollment Australia	1 Participants n=193 Participants	0 Participants n=193 Participants	1 Participants n=386 Participants
Region of Enrollment Germany	1 Participants n=193 Participants	2 Participants n=193 Participants	3 Participants n=386 Participants
Region of Enrollment Spain	9 Participants n=193 Participants	7 Participants n=193 Participants	16 Participants n=386 Participants

PRIMARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months)

Population: All randomized participants (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide =8, Irinotecan +Temozolomide = 3.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Progression Free Survival (PFS) Assessed by Blinded Independent Review Committee (BIRC) by Bayesian Analysis	NA Months Posterior mean estimator of median PFS time = 5.97, 80% credible interval= (4.44 to 7.72)	NA Months Posterior mean estimator of median PFS time = 3.02, 80% credible interval= (2.04 to 4.19)	—

PRIMARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months)

Population: All randomized participants (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide =8, Irinotecan +Temozolomide = 3.

PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using frequentist analysis.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
PFS Assessed by BIRC by Frequentist Analysis	2.79 Months Interval 1.74 to 13.32	2.89 Months Interval 1.25 to 5.13	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months)

Population: All randomized participants (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide =6, Irinotecan +Temozolomide = 3.

PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using Bayesian analysis and are reported as posterior mean along with its 80% credible interval.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
PFS Assessed by Investigator by Bayesian Analysis	NA Months Posterior mean estimator of median PFS time= 5.94, 80% credible interval= (4.49 to 7.61)	NA Months Posterior mean estimator of median PFS time= 3.90, 80% credible interval= (2.63 to 5.41)	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months)

Population: All randomized participants (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide =6, Irinotecan +Temozolomide = 3.

PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever was later). Results were obtained using frequentist analysis.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
PFS Assessed by Investigator by Frequentist Analysis	2.93 Months Interval 1.74 to 10.59	3.81 Months Interval 1.41 to 6.94	—

SECONDARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Up to 26.37 months)

Population: All randomized participants (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide = 15, Irinotecan +Temozolomide = 7.

OS was defined as the time from date of randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Overall Survival (OS)	21.21 Months Interval 9.17 to Upper limit of the 95% Confidence Interval (CI) was not estimable due to the high censoring rate.	6.94 Months Interval 5.13 to Upper limit of the 95% Confidence Interval (CI) was not estimable due to the high censoring rate.	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months)

Population: All randomized participants.

ORR was defined as the number of participants who achieved the best overall response of complete response (CR) or partial response (PR) as per RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) Assessed by BIRC	10.0 Percentage of Participants Interval 2.1 to 26.5	25.0 Percentage of Participants Interval 7.3 to 52.4	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months)

Population: All randomized participants.

ORR was defined as the number of participants who achieved the best overall response of CR or PR as per RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
ORR: Percentage of Participants Who Achieved a CR or PR Assessed by Investigator	16.7 Percentage of Participants Interval 5.6 to 34.7	18.8 Percentage of Participants Interval 4.1 to 45.7	—

SECONDARY outcome

Timeframe: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 10.7 Months)

Population: All randomized participants who received at least one dose of study drug and who had CR or PR responses (including the censored participants). Number of participants censored in Abemaciclib + Irinotecan +Temozolomide =1, Irinotecan +Temozolomide = 3.

DoR was defined as the time from the date that measurement criteria for CR or PR (whichever was first recorded) were first met until the first date that recurrent disease or documented disease progression was observed per RECIST v1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. DoR was calculated for participants with only PR or CR. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants with an observed CR or PR, no confirmed disease progression per RECIST v1.1 criteria, and no death due to any cause were censored at the time of the last adequate post-baseline scan.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=3 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=4 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Duration of Response (DoR) Assessed by BIRC	NA Months Estimation of the median and the 95% confidence interval limits (lower and upper) was not possible due to insufficient number of PR or CR responses.	NA Months Estimation of the median and the 95% confidence interval limits (lower and upper) was not possible due to insufficient number of PR or CR responses.	—

SECONDARY outcome

Timeframe: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 12.7 Months)

DoR was defined as the time from the date that measurement criteria for CR or PR (whichever was first recorded) were first met until the first date that recurrent disease or documented disease progression was observed, per RECIST v1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. DoR was calculated for participants with only PR or CR. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants with an observed CR or PR, no confirmed disease progression per RECIST v1.1 criteria, and no death due to any cause were censored at the time of the last adequate post-baseline scan.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=5 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=3 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
DoR Assessed by Investigator	NA Months Estimation of the median and the 95% confidence interval limits (lower and upper) was not possible due to insufficient number of PR or CR responses.	NA Months Estimation of the median and the 95% confidence interval limits (lower and upper) was not possible due to insufficient number of PR or CR responses.	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months)

Population: All randomized participants.

Disease control rate (DCR) was the percentage of participants with a best overall response of CR, PR, SD or Non-CR/Non-PD as defined by RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Non-CR/Non-PD was defined as persistence of one or more non-target lesions and/or maintained tumor marker levels, but without sufficient progression to be considered PD and without complete disappearance to be CR.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Percentage of Participants With a Best Overall Response of CR, PR, Stable Disease (SD) or Non-CR/Non-PD: Disease Control Rate (DCR) Assessed by BIRC	60.0 Percentage of Participants Interval 40.6 to 77.3	50.0 Percentage of Participants Interval 24.7 to 75.4	—

SECONDARY outcome

Timeframe: From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months)

Population: All randomized participants.

DCR was the percentage of participants with a best overall response of CR, PR, or SD as defined by RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease for target lesions, no progression of non-target lesions, and no appearance of new lesions.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=30 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=16 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Percentage of Participants With a Best Overall Response of CR, PR or SD: DCR Assessed by Investigator	60.0 Percentage of Participants Interval 40.6 to 77.3	56.3 Percentage of Participants Interval 29.9 to 80.3	—

SECONDARY outcome

Timeframe: Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1; End of irinotecan infusion on Cycle 2 Day 1 and Cycle 4 Day 1

Population: All randomized participants who received at least one dose of abemaciclib and had evaluable PK data.

PK: Cmin of Abemaciclib were reported.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=29 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib	118 nanogram per milliliter Geometric Coefficient of Variation 95	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 through Cycle 3 (21-day cycles)

Population: All randomized participants who received at least one dose of abemaciclib and had evaluable data for this outcome. Per protocol, data were summarized by responses provided by participants and/or caregivers on the acceptability of the abemaciclib received on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1. Here, 'Number Analyzed' refers to the number of participants or caregivers who provided responses.

Participants were evaluated for abemaciclib acceptability by asking a question - " Was it easy or difficult for the study participant to swallow the abemaciclib today?" Participants or their caregivers or both could respond using the following possible answers: "Very difficult", "difficult", "neither easy nor difficult", "easy", or "very easy". Acceptability was assessed for formulations: tablets, oral granules, and dispersed tablets.

Outcome measures

Outcome measures
Measure	Abemaciclib + Irinotecan +Temozolomide n=29 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=26 Participants Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Abemaciclib (Cycle 3 Day 1) n=18 Participants Participants received 55 mg/m² abemaciclib administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years on Day 1 Cycle 3 were reported in this arm.
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Caregiver Responses · Very difficult to swallow	—	0 Participants	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet Dispersed: Caregiver Responses · Very easy to swallow	0 Participants	1 Participants	1 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet Dispersed: Caregiver Responses · Easy to swallow	1 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet Dispersed: Caregiver Responses · Neither easy nor difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet Dispersed: Caregiver Responses · Difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet Dispersed: Caregiver Responses · Very difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Participant Responses · Very easy to swallow	15 Participants	16 Participants	11 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Participant Responses · Easy to swallow	4 Participants	1 Participants	2 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Participant Responses · Neither easy nor difficult to swallow	2 Participants	1 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Participant Responses · Difficult to swallow	1 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Participant Responses · Very difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Caregiver Responses · Very easy to swallow	5 Participants	7 Participants	4 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Caregiver Responses · Easy to swallow	1 Participants	0 Participants	1 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Caregiver Responses · Neither easy nor difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Caregiver Responses · Difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Tablet: Caregiver Responses · Very difficult to swallow	0 Participants	0 Participants	0 Participants
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Participant Responses · Very easy to swallow	1 Participants	—	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Participant Responses · Easy to swallow	0 Participants	—	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Participant Responses · Neither easy nor difficult to swallow	0 Participants	—	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Participant Responses · Difficult to swallow	0 Participants	—	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Participant Responses · Very difficult to swallow	0 Participants	—	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Caregiver Responses · Very easy to swallow	—	1 Participants	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Caregiver Responses · Easy to swallow	—	0 Participants	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Caregiver Responses · Neither easy nor difficult to swallow	—	0 Participants	—
Abemaciclib Product Acceptability Participant Who Received Abemaciclib Oral Granules: Caregiver Responses · Difficult to swallow	—	0 Participants	—

Adverse Events

Abemaciclib + Irinotecan +Temozolomide

Serious events: 12 serious events

Other events: 30 other events

Deaths: 15 deaths

Irinotecan +Temozolomide

Serious events: 5 serious events

Other events: 15 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Abemaciclib + Irinotecan +Temozolomide n=30 participants at risk Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Abemaciclib: 55 mg/m², administered orally BID for \<18 years or 100 mg administered orally BID for ≥18 years. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.	Irinotecan +Temozolomide n=15 participants at risk Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Blood and lymphatic system disorders Febrile neutropenia	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain	10.0% 3/30 • Number of events 3 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/30 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.7% 1/15 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pain	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pyrexia	6.7% 2/30 • Number of events 2 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	13.3% 2/15 • Number of events 2 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Catheter site infection	0.00% 0/30 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.7% 1/15 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Clostridial infection	0.00% 0/30 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.7% 1/15 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Clostridium difficile colitis	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Clostridium difficile infection	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	10.0% 3/30 • Number of events 3 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Enterocolitis	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Vomiting	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Metabolic acidosis	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Enterocolitis infectious	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Herpes zoster reactivation	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Rhinovirus infection	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Sepsis	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/30 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.7% 1/15 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Agitation	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Mania	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Mental status changes	3.3% 1/30 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/15 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/30 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.7% 1/15 • Number of events 1 • Baseline up to end of follow-up (up to 26.37 months) All-Cause Mortality: All randomized participants. Serious and other adverse events: All randomized participants who received at least one dose of study drug; Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.