Trial Outcomes & Findings for An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma (Study E7389-J081-217) (NCT NCT01458249)

Last Updated: 2016-03-28

Results Overview

The PFR at 12 weeks was the percentage of participants with progression-free survival (success) measured as a binary variable based on the tumor response assessed at Week 12 after the start of study treatment. Participants were considered a success if one radiological evaluation performed at least Week 12 after start of therapy indicated stable disease (SD), or complete response (CR) or partial response (PR), as defined according to Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1); all other cases were considered as failures (including disease progression or death before the Week 12 evaluation, or had unknown disease status at Week 12). If new anticancer treatments were started before the Week 12 evaluation, participants were considered failures. A 2-sided 90% confidence interval (CI) was calculated using the exact method of binomial distribution.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Week 12

Results posted on

2016-03-28

Participant Flow

Participant milestones

Participant milestones
Measure	All Treated Participants (Arm 1 and Arm 2) Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks).
Overall Study STARTED	52
Overall Study Participants Treated	51
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	All Treated Participants (Arm 1 and Arm 2) Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks).
Overall Study Not treated	1
Overall Study Adverse Event	4
Overall Study Other	2
Overall Study Ongoing	1

Baseline Characteristics

An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma (Study E7389-J081-217)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)	Total n=51 Participants Total of all reporting groups
Age, Continuous	51.4 Years STANDARD_DEVIATION 12.11 • n=5 Participants	50.4 Years STANDARD_DEVIATION 12.44 • n=7 Participants	51.1 Years STANDARD_DEVIATION 12.10 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	6 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Full analysis set included all participants who received at least one dose of study drug. This was the primary analysis set for all efficacy evaluations. Arm 1 included all participants with ADI or LMS. Arm 2 included all participants with soft tissue sarcomas other than ADI or LMS (OTH).

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Progression-free Rate at 12 Weeks (PFR12wks)	60.0 Percentage of participants Interval 44.7 to 74.0	31.3 Percentage of participants Interval 13.2 to 54.8

SECONDARY outcome

Timeframe: Cycle 1 (Day 1) to progressive disease (PD) or death, or date of study cutoff (14 Nov 2014) up to 3 years

Progression-free survival was defined as the time from the date of treatment start to the first documented date of event (disease progression or death from any cause, whichever occurred first). PFS was assessed every six weeks (until disease progression was confirmed, or sooner, if clinically indicated) and was based on Investigator and Independent Review Committee (IRC) assessments according to RECIST v1.1. Disease progression was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors and defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method was used to construct a log-log-transformed 95% CI.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Progression-Free Survival (PFS)	5.52 Months Interval 2.79 to 8.18	2.01 Months Interval 1.22 to 4.07

SECONDARY outcome

Timeframe: Cycle 1 (Day 1) to death, or date of study cutoff, (14 Nov 2014), up to 3 years

Overall survival was defined as the time from the date of treatment start to the date of death from any cause. Participants were followed for survival every twelve weeks after PD. In the absence of confirmation of death, participants were censored either at the date that the participant was last known alive or the date of study cutoff, whichever came earlier. Participants censored before database cutoff included those who were lost to follow up and who withdrew consent. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method is used to construct a log-log-transformed 95% CI.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Overall Survival (OS)	16.95 Months Interval 11.01 to 20.47	7.64 Months Interval 3.84 to 16.13

SECONDARY outcome

Timeframe: Date of CR or PR to the date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years

Objective response rate was defined as the percentage of participants who had a best overall rate (BOR) of CR or PR. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. The BOR of CR and PR in this study required confirmation by a subsequent assessment of response at least four weeks (28 days) later. CR and PR were determined by the Investigator and IRC using RECIST v1.1 for target lesions assessed by MRI/CT scans. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A 95% CI was calculated using exact method of binomial distribution.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Objective Response Rate (ORR)	0 Percentage of participants Interval 0.0 to 10.0	0 Percentage of participants Interval 0.0 to 20.6

SECONDARY outcome

Timeframe: Date of CR, PR, or SD to date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years

Disease control rate was defined as the percentage of participants who had BOR of CR + PR + SD. BOR of SD must have manifested at least five weeks (35 days) after the first dose of study treatment. Tumor assessment was performed at Week 6 and Week 12 after the start of treatment, and every six weeks thereafter. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started. A 95% CI was calculated using exact method of binomial distribution.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Disease Control Rate (DCR)	80.0 Percentage of participants Interval 63.1 to 91.6	50.0 Percentage of participants Interval 24.7 to 75.3

SECONDARY outcome

Timeframe: First dose of study treatment to the date of CR, PR, or dSD to date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years

CBR was defined as the percentage of participants who had a BOR of CR + PR + dSD (duration of SD greater than or equal to 11 weeks \[77 days\] after the first dose of study treatment). Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. For participants whose BOR was SD, the duration of SD was defined as the time from the date of the first dose of study treatment to the first documented PD or death, whichever occurred first (i.e., same definition of PFS). If the dSD was censored at a time less than 11 weeks, the participant was considered as not having a clinical benefit. A 95% CI was calculated using exact method of binomial distribution.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Clinical Benefit Rate (CBR)	74.3 Percentage of participants Interval 56.7 to 87.5	50.0 Percentage of participants Interval 24.7 to 75.3

SECONDARY outcome

Timeframe: Date of dSD to date of PD or death, whichever is first, or date of study cutoff (24 Nov 2014), up to 3 years

Durable stable disease rate was defined as the percentage of participants who manifested durable stable disease (the duration of stable disease for greater than or equal to eleven weeks) and was estimated based on the tumor response assessments performed according to RECIST v1.1. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. A 2-sided 95% CI was calculated using the exact method of binomial distribution.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Durable Stable Disease (SD) Rate (dSDR)	74.3 Percentage of participants Interval 56.7 to 87.5	50.0 Percentage of participants Interval 24.7 to 75.3

SECONDARY outcome

Timeframe: Date of CR, PR, SD to PD or death of any cause, whichever is first, or date of study cutoff (14 Nov 2014), or up to 3 years

The best overall response categories (CR, PR, SD \[including non-CR/non-PD\], PD, not evaluable \[NE\], and unknown \[UNK\]) were derived based on time point tumor responses during the study as assessed by the IRC as well as the investigator. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. BOR of SD must have occurred at least 35 days (at least 5 weeks) after the first dose of study drug. If a participant had a BOR of non-CR/non-PD, the participant's BOR was grouped with the SD category.

Outcome measures

Outcome measures
Measure	Arm 1: Participants With ADI or LMS n=35 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Adipocyte sarcoma (ADI) or Leiomyosarcoma (LMS)	Arm 2: Participants With OTH n=16 Participants Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks). Other types of eligible soft tissue sarcoma (OTH)
Best Overall Response (BOR) Complete response	0 Percentage of participants	0 Percentage of participants
Best Overall Response (BOR) Partial response	0 Percentage of participants	0 Percentage of participants
Best Overall Response (BOR) Stable disease	80.0 Percentage of participants	50.0 Percentage of participants
Best Overall Response (BOR) Progressive disease	20.0 Percentage of participants	50.0 Percentage of participants
Best Overall Response (BOR) Not evaluable	0 Percentage of participants	0 Percentage of participants
Best Overall Response (BOR) Unknown	0 Percentage of participants	0 Percentage of participants

Adverse Events

All Treated Participants (Arm 1 and Arm 2)

Serious events: 15 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Treated Participants (Arm 1 and Arm 2) n=51 participants at risk Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks).
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Cardiac disorders Cardiac failure	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Eye disorders Cataract	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Ileus	3.9% 2/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Hepatobiliary disorders Hepatic haemorrhage	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Infectious pleural effusion	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Pneumonia	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Streptococcal infection	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour embolism	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Renal and urinary disorders Hydronephrosis	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 1/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.

Other adverse events

Other adverse events
Measure	All Treated Participants (Arm 1 and Arm 2) n=51 participants at risk Eribulin mesylate was administered at a dose of 1.4 mg/m\^2 as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days (3 weeks).
Blood and lymphatic system disorders Anaemia	47.1% 24/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Blood and lymphatic system disorders Febrile neutropenia	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Blood and lymphatic system disorders Leukopenia	100.0% 51/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Blood and lymphatic system disorders Lymphopenia	78.4% 40/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Blood and lymphatic system disorders Neutropenia	98.0% 50/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Blood and lymphatic system disorders Thrombocytopenia	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Cardiac disorders Tachycardia	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Abdominal pain upper	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Cheilitis	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Constipation	31.4% 16/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Diarrhoea	13.7% 7/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Nausea	41.2% 21/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Stomatitis	25.5% 13/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Gastrointestinal disorders Vomiting	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
General disorders Fatigue	17.6% 9/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
General disorders Malaise	39.2% 20/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
General disorders Oedema peripheral	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
General disorders Pyrexia	41.2% 21/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Hepatobiliary disorders Hepatic function abnormal	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Gingivitis	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Nasopharyngitis	21.6% 11/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Upper respiratory tract infection	21.6% 11/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Infections and infestations Urinary tract infection	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Injury, poisoning and procedural complications Fall	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Alanine aminotransferase increased	27.5% 14/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Aspartate aminotransferase increased	25.5% 13/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Blood alkaline phosphatase increased	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Blood creatine phosphokinase increased	15.7% 8/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Blood lactate dehydrogenase increased	21.6% 11/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations C-reactive protein increased	11.8% 6/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Investigations Weight decreased	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Decreased appetite	23.5% 12/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hyperlipidaemia	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypertriglyceridaemia	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypoalbuminaemia	19.6% 10/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypocalcaemia	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypokalaemia	11.8% 6/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypophosphataemia	15.7% 8/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Metabolism and nutrition disorders Hypoproteinaemia	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Musculoskeletal and connective tissue disorders Arthralgia	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Musculoskeletal and connective tissue disorders Back pain	13.7% 7/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Musculoskeletal and connective tissue disorders Osteoarthritis	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Musculoskeletal and connective tissue disorders Pain in extremity	7.8% 4/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	41.2% 21/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Nervous system disorders Dysgeusia	23.5% 12/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Nervous system disorders Headache	11.8% 6/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Nervous system disorders Neuropathy peripheral	31.4% 16/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Nervous system disorders Peripheral sensory neuropathy	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Psychiatric disorders Insomnia	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Renal and urinary disorders Proteinuria	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Respiratory, thoracic and mediastinal disorders Cough	11.8% 6/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.8% 5/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Skin and subcutaneous tissue disorders Alopecia	27.5% 14/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Skin and subcutaneous tissue disorders Eczema	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Skin and subcutaneous tissue disorders Rash	11.8% 6/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.
Vascular disorders Hypertension	5.9% 3/51 • All adverse events (AEs) were collected beginning from the time of informed consent through 30 days after the last dose of study drug or until resolution, whichever came first. Participants were followed for an average of 18 weeks. Safety data was based on the safety analysis set which included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation. Treatment-emergent Serious AEs (SAEs) and non-serious AEs are reported in the safety section.

Additional Information

Sun Asami

Eisai Co., Ltd.

Phone: +81-3-3817-5252

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER