Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors (NCT NCT03245450)

Last Updated: 2022-06-28

Results Overview

The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities \[DLTs\]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

40 participants

Primary outcome timeframe

First dose of study drug up to Cycle 1 (Cycle length=21 days)

Results posted on

2022-06-28

Participant Flow

Participants took part in the study at 22 investigative sites in France, Germany, Greece, Italy, Poland, Spain and United Kingdom from 05 March 2018 to 17 May 2021.

A total of 46 participants were screened, out of which 13 participants were treated in the Phase 1 and 27 participants were treated in Phase 2 (9 participants each in the relapsed/refractory rhabdomyosarcoma \[RMS\], non-rhabdomyosarcoma soft tissue sarcoma \[NRSTS\], and Ewing sarcoma \[EWS\] cohorts).

Participant milestones

Participant milestones
Measure	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 (milligram per square meter) intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 100 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Study STARTED	3	4	3	3	9	9	9
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	4	3	3	9	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 (milligram per square meter) intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 100 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Study Radiological disease progression	3	3	2	2	7	6	6
Overall Study Clinical disease progression	0	0	1	0	0	2	0
Overall Study Other	0	0	0	1	1	1	1
Overall Study Withdrawal by Subject	0	1	0	0	0	0	0
Overall Study Adverse Event	0	0	0	0	1	0	2

Baseline Characteristics

Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 100 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Total n=40 Participants Total of all reporting groups
Age, Continuous Phase 1	10.94 years STANDARD_DEVIATION 6.583 • n=3 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	7.33 years STANDARD_DEVIATION 2.540 • n=4 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	13.97 years STANDARD_DEVIATION 4.231 • n=3 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	8.06 years STANDARD_DEVIATION 4.997 • n=3 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	—	—	—	9.87 years STANDARD_DEVIATION 4.842 • n=13 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.
Age, Continuous Phase 2	—	—	—	—	11.05 years STANDARD_DEVIATION 3.845 • n=9 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	12.71 years STANDARD_DEVIATION 4.348 • n=9 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	11.59 years STANDARD_DEVIATION 3.753 • n=9 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.	11.78 years STANDARD_DEVIATION 3.899 • n=27 Participants • Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.
Age, Customized Children (2-11 years)	1 Participants n=3 Participants	4 Participants n=4 Participants	1 Participants n=3 Participants	2 Participants n=3 Participants	5 Participants n=9 Participants	3 Participants n=9 Participants	4 Participants n=9 Participants	20 Participants n=40 Participants
Age, Customized Adolescents (12-17 years)	2 Participants n=3 Participants	0 Participants n=4 Participants	2 Participants n=3 Participants	1 Participants n=3 Participants	4 Participants n=9 Participants	6 Participants n=9 Participants	5 Participants n=9 Participants	20 Participants n=40 Participants
Sex: Female, Male Female	2 Participants n=3 Participants	1 Participants n=4 Participants	2 Participants n=3 Participants	2 Participants n=3 Participants	5 Participants n=9 Participants	2 Participants n=9 Participants	5 Participants n=9 Participants	19 Participants n=40 Participants
Sex: Female, Male Male	1 Participants n=3 Participants	3 Participants n=4 Participants	1 Participants n=3 Participants	1 Participants n=3 Participants	4 Participants n=9 Participants	7 Participants n=9 Participants	4 Participants n=9 Participants	21 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=3 Participants	1 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	1 Participants n=9 Participants	0 Participants n=9 Participants	2 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=3 Participants	3 Participants n=4 Participants	3 Participants n=3 Participants	3 Participants n=3 Participants	9 Participants n=9 Participants	8 Participants n=9 Participants	9 Participants n=9 Participants	38 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=3 Participants	0 Participants n=4 Participants	1 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	1 Participants n=9 Participants	0 Participants n=9 Participants	1 Participants n=40 Participants
Race (NIH/OMB) White	3 Participants n=3 Participants	4 Participants n=4 Participants	2 Participants n=3 Participants	3 Participants n=3 Participants	5 Participants n=9 Participants	8 Participants n=9 Participants	8 Participants n=9 Participants	33 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	4 Participants n=9 Participants	0 Participants n=9 Participants	1 Participants n=9 Participants	5 Participants n=40 Participants

PRIMARY outcome

Timeframe: First dose of study drug up to Cycle 1 (Cycle length=21 days)

Population: The Dose Evaluable Set (DES) for Phase 1 included all the participants who completed Cycle 1 treatment and were evaluated for DLTs and those who discontinued treatment during Cycle 1 due to DLTs.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=12 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride Eribulin Mesilate	1.4 mg/m^2	—	—	—	—	—	—
Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride Irinotecan Hydrochloride	40 mg/m^2	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months

Population: Full analysis set included all participants who received at least 1 dose of either study drug.

ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=9 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 2: Objective Response Rate (ORR)	11.1 percentage of participants 90% Confidence Interval 0.6 • Interval 0.6 to 42.9	11.1 percentage of participants 90% Confidence Interval 0.6 • Interval 0.6 to 42.9	11.1 percentage of participants 90% Confidence Interval 0.6 • Interval 0.6 to 42.9	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug up to approximately 2 years 4 months

Population: Safety analysis set included all participants who received at least 1 dose of either study drug.

A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	3 Participants	4 Participants	3 Participants	3 Participants	9 Participants	9 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to approximately 2 years and 4 months

Population: Safety analysis set included all participants who received at least 1 dose of either study drug.

SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Number of Participants With Serious Adverse Event (SAE)	1 Participants	3 Participants	0 Participants	1 Participants	5 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Population: PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Eribulin	369.3 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 58.0 • Interval 58.0 to	179.4 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 136.1 • Interval 136.1 to	348.7 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 25.0 • Interval 25.0 to	323.3 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 20.6 • Interval 20.6 to	—	—	—
Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Irinotecan	538.8 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 165.9 • Interval 165.9 to	399.5 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 19.1 • Interval 19.1 to	1168.1 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 39.8 • Interval 39.8 to	1555.4 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 39.5 • Interval 39.5 to	—	—	—
Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Active Metabolite SN-38	6.518 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 9.4 • Interval 9.4 to	17.170 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 39.7 • Interval 39.7 to	25.409 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 51.6 • Interval 51.6 to	18.614 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 74.3 • Interval 74.3 to	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Population: PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38 Eribulin	0.080 hours Full Range 0.03 • Interval 0.03 to 0.22	0.135 hours Full Range 0.03 • Interval 0.03 to 1.0	0.080 hours Full Range 0 • Interval 0.0 to 0.12	0.050 hours Full Range 0.01 • Interval 0.01 to 0.12	—	—	—
Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38 Irinotecan	0.250 hours Full Range 0.07 • Interval 0.07 to 0.42	0.305 hours Full Range 0 • Interval 0.0 to 24.0	0.300 hours Full Range 0.03 • Interval 0.03 to 0.33	0.170 hours Full Range 0.13 • Interval 0.13 to 0.25	—	—	—
Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38 Active Metabolite SN-38	0.420 hours Full Range 0.25 • Interval 0.25 to 1.03	0.305 hours Full Range 0 • Interval 0.0 to 24.0	0.330 hours Full Range 0.3 • Interval 0.3 to 0.53	0.250 hours Full Range 0.13 • Interval 0.13 to 0.55	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Population: PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.

Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 20 mg/m\^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 40 mg/m\^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=2 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38 Eribulin	27.50 hours Interval 26.5 to 27.7	34.70 hours Interval 32.9 to 40.4	30.00 hours Interval 23.4 to 43.3	25.30 hours Interval 22.1 to 28.5	—	—	—
Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38 Irinotecan	—	—	5.140 hours Interval 5.1 to 9.61	4.430 hours Interval 3.95 to 5.08	—	—	—
Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38 Metabolite SN-38	—	—	12.000 hours Interval 9.9 to 13.9	10.390 hours Interval 9.68 to 11.1	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 20 mg/m\^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 40 mg/m\^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=2 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, Total Clearance (CL) of Eribulin and Irinotecan Eribulin	3.1781 liter per hour (L/h) Geometric Coefficient of Variation 43.9	2.4581 liter per hour (L/h) Geometric Coefficient of Variation 8.0	2.9060 liter per hour (L/h) Geometric Coefficient of Variation 32.8	1.7521 liter per hour (L/h) Geometric Coefficient of Variation 136.6	—	—	—
Phase 1, Total Clearance (CL) of Eribulin and Irinotecan Irinotecan	—	—	27.27 liter per hour (L/h) Geometric Coefficient of Variation 23.2	30.30 liter per hour (L/h) Geometric Coefficient of Variation 60.7	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 20 mg/m\^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 40 mg/m\^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=2 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan Eribulin	124.70 liter Geometric Coefficient of Variation 41.5	126.96 liter Geometric Coefficient of Variation 18.1	130.78 liter Geometric Coefficient of Variation 35.9	63.35 liter Geometric Coefficient of Variation 101.8	—	—	—
Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan Irinotecan	—	—	248.5 liter Geometric Coefficient of Variation 16.1	195.1 liter Geometric Coefficient of Variation 69.0	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Population: PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Eribulin	422.5 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 40.0 • Interval 40.0 to	403.7 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 32.1 • Interval 32.1 to	616.9 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 66.1 • Interval 66.1 to	603.5 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 87.3 • Interval 87.3 to	—	—	—
Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Irinotecan	1812.6 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 13.5 • Interval 13.5 to	3686.1 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 36.4 • Interval 36.4 to	4693.9 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 66.1 • Interval 66.1 to	3633.7 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 38.9 • Interval 38.9 to	—	—	—
Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 Metabolite SN-38	68.00 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 19.7 • Interval 19.7 to	145.04 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 11.6 • Interval 11.6 to	138.22 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 42.2 • Interval 42.2 to	65.47 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 153.2 • Interval 153.2 to	—	—	—

SECONDARY outcome

Timeframe: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 20 mg/m\^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m\^2 + irinotecan 40 mg/m\^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=3 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=2 Participants Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38 Metabolite SN-38	—	—	169.0 h*ng/mL Geometric Coefficient of Variation 51.4	149.4 h*ng/mL Geometric Coefficient of Variation 4.3	—	—	—
Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38 Eribulin	438.1 h*ng/mL Geometric Coefficient of Variation 39.0	506.0 h*ng/mL Geometric Coefficient of Variation 16.6	666.9 h*ng/mL Geometric Coefficient of Variation 69.0	576.9 h*ng/mL Geometric Coefficient of Variation 133.6	—	—	—
Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38 Irinotecan	—	—	5036.1 h*ng/mL Geometric Coefficient of Variation 70.9	3698.5 h*ng/mL Geometric Coefficient of Variation 39.2	—	—	—

SECONDARY outcome

Timeframe: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months

Population: Full analysis set included all participants who received at least 1 dose of either study drug.

PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=9 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 2: Progression Free Survival (PFS)	2.69 months 90% Confidence Interval 1.28 • Interval 1.28 to 8.87	1.35 months 90% Confidence Interval 1.15 • Interval 1.15 to 2.79	6.70 months 90% Confidence Interval 1.38 • Interval 1.38 to 8.84	—	—	—	—

SECONDARY outcome

Timeframe: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months

Population: Full analysis set included all participants who received at least 1 dose of either study drug.

CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than \[\>\] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=5 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=3 Participants Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=5 Participants Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Phase 2: Clinical Benefit Rate (CBR)	55.6 percentage of participants 90% Confidence Interval 25.1 • Interval 25.1 to 83.1	33.3 percentage of participants 90% Confidence Interval 9.8 • Interval 9.8 to 65.5	55.6 percentage of participants 90% Confidence Interval 25.1 • Interval 25.1 to 83.1	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)

Population: PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885)."Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=561 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Model Predicted Apparent Total Body Clearance (CL) of Eribulin	2.89 L/hr Interval 2.75 to 3.03	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)

Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.

Outcome measures

Outcome measures
Measure	Phase 1: All Participants n=561 Participants All participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2 or 40 mg/m\^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m\^2 or 125 mg/m\^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Volume of Distribution Estimates From the Population PK Model for Eribulin V1	4.08 liter Interval 3.87 to 4.29	—	—	—	—	—	—
Volume of Distribution Estimates From the Population PK Model for Eribulin V2	2.03 liter Interval 1.79 to 2.27	—	—	—	—	—	—
Volume of Distribution Estimates From the Population PK Model for Eribulin V3	106 liter Interval 101.0 to 111.0	—	—	—	—	—	—

Adverse Events

Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2

Serious events: 3 serious events

Other events: 4 other events

Deaths: 2 deaths

Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2

Serious events: 5 serious events

Other events: 9 other events

Deaths: 4 deaths

Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2

Serious events: 4 serious events

Other events: 9 other events

Deaths: 3 deaths

Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2

Serious events: 3 serious events

Other events: 9 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 100 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	50.0% 2/4 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Bacteraemia	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Device related infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Sepsis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Malnutrition	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months

Other adverse events

Other adverse events
Measure	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=4 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 100 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 n=3 participants at risk Participants received eribulin mesilate 1.4 mg/m\^2 and irinotecan hydrochloride 125 mg/m\^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with RMS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.	Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with NRSTS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.	Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 n=9 participants at risk Participants with EWS received eribulin mesilate 1.4 mg/m\^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m\^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Psychiatric disorders Agitation	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Psychiatric disorders Anxiety	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Psychiatric disorders Depressed mood	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Psychiatric disorders Negative thoughts	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Psychiatric disorders Tearfulness	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	50.0% 2/4 • Number of events 14 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 6 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 9 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 29 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Leukopenia	33.3% 1/3 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 14 • From first dose of study drug up to approximately 2 year 4 months	66.7% 2/3 • Number of events 15 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 12 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 32 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Neutropenia	100.0% 3/3 • Number of events 39 • From first dose of study drug up to approximately 2 year 4 months	50.0% 2/4 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	100.0% 3/3 • Number of events 18 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 12 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 15 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 10 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 52 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 17 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	77.8% 7/9 • Number of events 9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Abdominal pain upper	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	66.7% 2/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Constipation	66.7% 2/3 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 12 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 24 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 11 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	66.7% 2/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	66.7% 6/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Oral pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Toothache	33.3% 1/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Vomiting	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	50.0% 2/4 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	100.0% 3/3 • Number of events 10 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	66.7% 6/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months
General disorders Asthenia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
General disorders Catheter site pain	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
General disorders Non-cardiac chest pain	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Conjunctivitis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Rhinitis	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Tonsillitis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Vascular device infection	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Procedural nausea	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Urostomy complication	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Alanine aminotransferase increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 10 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months
Investigations C-reactive protein increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Lymphocyte count decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months
Investigations Neutrophil count decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	75.0% 3/4 • Number of events 8 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	66.7% 2/3 • Number of events 7 • From first dose of study drug up to approximately 2 year 4 months	66.7% 6/9 • Number of events 21 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 22 • From first dose of study drug up to approximately 2 year 4 months	55.6% 5/9 • Number of events 46 • From first dose of study drug up to approximately 2 year 4 months
Investigations Weight decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Investigations White blood cell count decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	75.0% 3/4 • Number of events 7 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 20 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 6 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Hypophosphataemia	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	44.4% 4/9 • Number of events 6 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Paraesthesia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Psychiatric disorders Insomnia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	25.0% 1/4 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Skin oedema	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	33.3% 1/3 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Cardiac disorders Tachycardia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Ear and labyrinth disorders Ear pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Anal fissure	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Anal inflammation	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Aphthous ulcer	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Gingival pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Haematemesis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Haematochezia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Odynophagia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Proctalgia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months
Gastrointestinal disorders Tongue ulceration	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
General disorders Catheter site pruritus	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
General disorders Fatigue	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	33.3% 3/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months
General disorders Gait disturbance	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
General disorders Oedema peripheral	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
General disorders Pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Bacterial infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations COVID-19	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Device related infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Ear infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Herpes simplex	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Influenza	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Nasopharyngitis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Oral candidiasis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Pneumonia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Respiratory tract infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Infections and infestations Urinary tract infection	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Mouth injury	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood albumin decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood calcium decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood creatinine increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood phosphorus decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood potassium decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood sodium decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Blood urea increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Investigations Haematocrit decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 7 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Metamyelocyte count increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Myelocyte count increased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Investigations Red blood cell count decreased	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 7 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 10 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Metabolism and nutrition disorders Refeeding syndrome	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 5 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Neuralgia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 4 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Nervous system disorders Syncope	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Renal and urinary disorders Haematuria	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months
Renal and urinary disorders Urinary tract pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Allergic cough	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Leukonychia	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Papule	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	11.1% 1/9 • Number of events 1 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/4 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/3 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	0.00% 0/9 • From first dose of study drug up to approximately 2 year 4 months	22.2% 2/9 • Number of events 2 • From first dose of study drug up to approximately 2 year 4 months

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