Trial Outcomes & Findings for Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Participants With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS) (NCT NCT03441360)

Last Updated: 2022-10-05

Results Overview

Percentage of participants achieving a best objective response of partial response (PR) or complete response (CR) per RECIST 1.1, by up to 24 weeks after all participants have completed response assessment. Response assessment was determined by investigator. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

From date of randomization up to first documentation of disease progression (PD) or date of death, whichever occurred first (approximately 32 months)

Results posted on

2022-10-05

Participant Flow

Participants took part in the study at 38 investigative sites in the United States from 17 April 2018 to 21 January 2022.

A total of 24 participants were screened, of which 1 was screen failure and 23 participants were enrolled, out of which 21 participants were randomized and treated in the study and 2 were not treated due to withdrawal of consent and rapid disease progression (1 participant from each arm).

Participant milestones

Participant milestones
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS Pediatric participants with rhabdomyosarcoma (RMS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 milligrams per meter square (mg/m\^2). Participants continued to receive study therapy until progression of disease, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS Pediatric participants with Ewing sarcoma (EWS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Overall Study STARTED	8	8	5
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	8	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS Pediatric participants with rhabdomyosarcoma (RMS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 milligrams per meter square (mg/m\^2). Participants continued to receive study therapy until progression of disease, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS Pediatric participants with Ewing sarcoma (EWS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Overall Study Radiological disease progression	5	6	4
Overall Study Clinical disease progression	2	2	0
Overall Study Adverse Event	1	0	1

Baseline Characteristics

Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Participants With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Total n=21 Participants Total of all reporting groups
Age, Continuous	10.4 years STANDARD_DEVIATION 4.53 • n=5 Participants	11.8 years STANDARD_DEVIATION 5.57 • n=7 Participants	13.2 years STANDARD_DEVIATION 4.32 • n=5 Participants	11.6 years STANDARD_DEVIATION 4.80 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: From date of randomization up to first documentation of disease progression (PD) or date of death, whichever occurred first (approximately 32 months)

Population: The FAS included all participants who receive at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Percentage of Participants With Objective Response	0 percentage of participants Interval 0.0 to 36.9	0 percentage of participants Interval 0.0 to 36.9	0 percentage of participants Interval 0.0 to 52.2

SECONDARY outcome

Timeframe: From the time from the first dose date to the date of disease progression (PD) or date of death, whichever occurred first (up to approximately 32 months)

Population: The FAS included all participants who receive at least 1 dose of study drug.

PFS was defined as the time from the first dose date to the date of PD or date of death (whichever occurred first). PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions was also considered progression). Data for this secondary endpoint was collected and analyzed up to the primary completion date (PCD). As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Progression-free Survival (PFS)	1.74 months Interval 1.12 to 2.86	1.30 months Interval 0.62 to 1.51	0.76 months Interval 0.59 to 4.04

SECONDARY outcome

Timeframe: From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)

Population: The safety analysis set included all participants who receive at least 1 dose of study drug.

An AE was any untoward medical occurrence in participant administered with an investigational product. An SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening; requires participant hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). A treatment-emergent adverse event (TEAE) was defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline) or (1) reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With Any Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) TEAEs	8 Participants	8 Participants	5 Participants
Number of Participants With Any Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	6 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to approximately 32 months

Population: The safety analysis set included all participants who receive at least 1 dose of study drug. Here number analyzed "n" are the participants who were evaluable for the outcome measure for given categories with non-missing data at both baseline and any post-baseline.

Laboratory results were graded using CTCAE Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences. Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Hemoglobin Decreased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Hemoglobin Decreased	3 Participants	4 Participants	3 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, Hemoglobin Decreased	0 Participants	1 Participants	2 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Hemoglobin Decreased	5 Participants	3 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Hemoglobin Decreased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Worst Post-Baseline Grade 2, Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, White blood cells decreased	0 Participants	1 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, White blood cells decreased	4 Participants	2 Participants	1 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, White blood cells decreased	2 Participants	1 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, White blood cells decreased	0 Participants	2 Participants	3 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, White blood cells decreased	2 Participants	1 Participants	1 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, White blood cells increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, White blood cells increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, White blood cells increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, White blood cells increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, White blood cells increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Lymphocyte count decreased	3 Participants	2 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Lymphocyte count decreased	1 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, Lymphocyte count decreased	1 Participants	0 Participants	3 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Lymphocyte count decreased	2 Participants	4 Participants	2 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Lymphocyte count decreased	1 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Lymphocyte count increased	8 Participants	4 Participants	5 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Lymphocyte count increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, Lymphocyte count increased	0 Participants	2 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Lymphocyte count increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Lymphocyte count increased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Neutrophil count decreased	1 Participants	0 Participants	1 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Neutrophil count decreased	1 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, Neutrophil count decreased	3 Participants	1 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Neutrophil count decreased	0 Participants	1 Participants	3 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Neutrophil count decreased	2 Participants	5 Participants	1 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 0, Platelet count decreased	5 Participants	6 Participants	3 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 1, Platelet count decreased	2 Participants	1 Participants	2 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 2, Platelet count decreased	1 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 3, Platelet count decreased	0 Participants	0 Participants	0 Participants
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value Baseline to Worst Post-baseline Grade 4, Platelet count decreased	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to approximately 32 months

Population: The safety analysis set included all participants who receive at least 1 dose of study drug.

Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to approximately 32 months

Population: The safety analysis set included all participants who receive at least 1 dose of study drug.

Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 32 months

Population: The safety analysis set included all participants who receive at least 1 dose of study drug. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure with non-missing data at both baseline and any post-baseline timepoint.

Reduced activities of daily living was assessed using the Lansky Play Performance Scale, where 100=fully active; 90=minor restrictions in strenuous physical activity; 80=active, gets tired more quickly; 70=greater restriction of play, less time spent in play activity; 60=up and around, active play minimal; quieter activities; 50=lying around much of the day; no active playing, all quiet play and activities; 40=mainly in bed; quiet activities; 30=bedbound; needs assistance even for quiet play; 20=sleeps often; play limited to very passive activities; 10=doesn't play or get out of bed; 5=unresponsive 0=dead. Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=7 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=7 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=4 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 50	1 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 60	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 70	2 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 80	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 90	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 70 to worst post-baseline score 100	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 50	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 60	1 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 70	1 Participants	1 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 80	0 Participants	2 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 90	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 80 to worst post-baseline score 100	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 50	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 60	0 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 70	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 80	1 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 90	0 Participants	2 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 90 to worst post-baseline score 100	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 50	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 60	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 70	1 Participants	1 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 80	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 90	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale Baseline score 100 to worst post-baseline score 100	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 32 months

Population: The safety analysis set included all participants who receive at least 1 dose of study drug. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure for the outcome measure with non-missing data at both baseline and any post-baseline timepoint.

Karnofsky performance status assessed as best and worst score change from baseline using Karnofsky performance criteria.Score classified participants based on functional impairment. Ranges from 0-100, lower score, worst survival for most serious illnesses, 100=normal;no complaints;no evidence of disease;90=able to carry on normal activity with effort,minor sign or symptoms of disease;80=normal activity with effort;some sign or symptoms of disease;70= cares for self;unable to carry on normal activity or do active work;60=requires occasional assistance,but able to care for most personal needs;50=requires considerable assistance;frequent medical care;40=disabled;requires special care; assistance;30=severely disabled;hospitalization indicated,although death is not imminent;20=very sick;hospitalization; 10=moribund;fatal processes progressively worsening;0=dead.Data for this endpoint was collected;analyzed up to PCD. As no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=1 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=1 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 70 to worst post-baseline score 50	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 70 to worst post-baseline score 60	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 70 to worst post-baseline score 70	1 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 70 to worst post-baseline score 80	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 70 to worst post-baseline score 90	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 50	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 60	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 70	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 80	0 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 90	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores Baseline score 90 to worst post-baseline score 100	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From day of first documentation of PR or CR to the day of disease progression or death (up to approximately 32 months)

Population: The FAS included all participants who receive at least 1 dose of study drug. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure however no participant with complete response or partial response were observed in this study.

DOR was defined as the time from the first date of documented PR or CR to the date of disease progression or date of death (whichever occurred first). CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the day of first dose to the day of death, up to approximately 45 months

Population: The FAS included all participants who receive at least 1 dose of study drug.

OS was defined as the time from the first dose date to the date of death.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 Participants Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 Participants Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 Participants Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Overall Survival (OS)	5.08 months Interval 1.74 to 6.47	6.95 months Interval 0.72 to 16.26	7.89 months Interval 2.5 to 29.8

Adverse Events

Eribulin Mesylate 1.4 mg/m^2: RMS

Serious events: 6 serious events

Other events: 8 other events

Deaths: 8 deaths

Eribulin Mesylate 1.4 mg/m^2: NRSTS

Serious events: 2 serious events

Other events: 8 other events

Deaths: 7 deaths

Eribulin Mesylate 1.4 mg/m^2: EWS

Serious events: 3 serious events

Other events: 5 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai, Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Eribulin Mesylate 1.4 mg/m^2: RMS n=8 participants at risk Pediatric participants with RMS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: NRSTS n=8 participants at risk Pediatric participants with non-rhabdomyosarcoma solid tumor sarcoma (NRSTS) received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.	Eribulin Mesylate 1.4 mg/m^2: EWS n=5 participants at risk Pediatric participants with EWS received eribulin mesylate as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants continued to receive study therapy until progression of disease, (per RECIST 1.1), exhibited no clinical benefit, intolerable toxicity, withdrawal of consent or termination of the study program, whichever occurred first.
Blood and lymphatic system disorders Neutropenia	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Infections and infestations Pneumonia	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Nervous system disorders Neuralgia	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	20.0% 1/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Blood and lymphatic system disorders Anaemia	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Cardiac disorders Cardiac tamponade	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Cardiac disorders Left ventricular dysfunction	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Cardiac disorders Pericardial effusion	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Cardiac disorders Sinus bradycardia	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	20.0% 1/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Gastrointestinal disorders Mouth haemorrhage	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
General disorders Pyrexia	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	20.0% 1/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	20.0% 1/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	20.0% 1/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Musculoskeletal and connective tissue disorders Muscular weakness	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Nervous system disorders Headache	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Nervous system disorders Seizure	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	12.5% 1/8 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)	0.00% 0/5 • From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)