Trial Outcomes & Findings for Eribulin in HER2 Negative Metastatic BrCa (NCT NCT01827787)

Last Updated: 2024-11-06

Results Overview

ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)

Results posted on

2024-11-06

Participant Flow

Participants were enrolled between May 2013 and March 2016.

Participant milestones

Participant milestones
Measure	Cohort 1: HR+/HER2- Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Overall Study STARTED	45	38
Overall Study COMPLETED	45	38
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Eribulin in HER2 Negative Metastatic BrCa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Total n=83 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Age, Continuous	59 years n=5 Participants	53 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	38 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	41 Participants n=5 Participants	35 Participants n=7 Participants	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	34 Participants n=7 Participants	76 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	45 participants n=5 Participants	38 participants n=7 Participants	83 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Score (ECOG PS) ECOG PS0	33 Participants n=5 Participants	26 Participants n=7 Participants	59 Participants n=5 Participants
Eastern Cooperative Oncology Group Performance Score (ECOG PS) ECOG PS1	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Eastern Cooperative Oncology Group Performance Score (ECOG PS) ECOG PS2	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Overall Response Rate (ORR)	35.6 percentage of participants Interval 24.0 to 49.0	13.2 percentage of participants Interval 5.0 to 26.0

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) PFS follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.

Population: The analysis dataset is comprised of all enrolled participants.

PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Progression-Free Survival (PFS)	6.2 months Interval 5.9 to 8.7	4.0 months Interval 3.5 to 4.8

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2).

Population: The analysis dataset is comprised of all enrolled participants.

TTR is defined as the time from first dose of study treatment until the earliest date that complete response (CR) or partial response (PR) based on RECIST 1.1 criteria is objectively documented. Non-CR, non-PR participants are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response requires 4 week or later confirmation and assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Time to First Response (TTR)	10.6 months Interval 1.7 to 14.9	NA months Interval 1.9 to 4.3 Median was not reached.

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) DOR follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.

Population: The analysis dataset is comprised of all enrolled participants.

DOR is defined as the that response criteria for CR or PR (whichever is recorded first) are first met until the date that PD or death from any cause is first objectively documented. Participants who do not have PD will be censored on date of last disease assessment.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Duration of Overall Response (DOR)	6.5 months Interval 1.8 to 12.3	1.9 months Interval 1.3 to 4.1

SECONDARY outcome

Timeframe: Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)

Population: The analysis dataset is comprised of all treated participants. Per protocol, the cohorts were combined for this analysis.

The percentage of treated participants experiencing grade 1-3 peripheral sensory neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=83 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy	36.1 percentage of participants Interval 27.4 to 45.7	—

SECONDARY outcome

Timeframe: Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)

Population: The analysis dataset is comprised of all treated participants.Per protocol, the cohorts were combined for this analysis.

TThe percentage of treated participants experiencing grade 1-3 peripheral motor neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=83 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy	22.9 percentage of participants Interval 15.5 to 31.7	—

SECONDARY outcome

Timeframe: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11

Population: The analysis dataset is comprised of all participants who completed both QOL assessments required to calculate change from baseline. Per protocol, the cohorts were combined for this analysis.

The FACT-BCS is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to breast cancer patients. (Brady MJ, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. JCO 1997; 15:974-86). The FACT-BCS has 9-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 36. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=83 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 2 Change from Baseline	1.0 units on a scale Standard Deviation 4.6	—
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 3 Change from Baseline	0.6 units on a scale Standard Deviation 5.1	—
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 5 Change from Baseline	0.1 units on a scale Standard Deviation 4.4	—
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 7 Change from Baseline	0.6 units on a scale Standard Deviation 3.2	—
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 9 Change from Baseline	1.8 units on a scale Standard Deviation 5.0	—
Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline Cycle 11 Change from Baseline	1.1 units on a scale Standard Deviation 2.9	—

SECONDARY outcome

Timeframe: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11

The FACT-Ntx is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to patients suffering from neurotoxicity. (Calhoun EA, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 2003; 13:741-8). The FACT-Ntx has 11-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 44. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=83 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 2 Change from Baseline	-0.1 units on a scale Standard Deviation 3.0	—
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 3 Change from Baseline	-0.3 units on a scale Standard Deviation 4.7	—
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 5 Change from Baseline	-1.6 units on a scale Standard Deviation 5.5	—
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 7 Change from Baseline	-4.5 units on a scale Standard Deviation 6.4	—
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 9 Change from Baseline	-1.8 units on a scale Standard Deviation 5.9	—
Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline Cycle 11 Change from Baseline	-1.6 units on a scale Standard Deviation 4.7	—

POST_HOC outcome

Timeframe: Overall median survival follow-up was 5.9 months including a maximum of 27 months for Cohort 1 and 15 months for Cohort 2.

OS based on Kaplan-Meier is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Outcome measures
Measure	Cohort 1: HR+/HER2- n=45 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 Participants Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Overall Survival	20 months Interval 20.0 to Follow-up is not long enough/Data is not mature to provide upper bound 90% CI.	11.3 months Interval 9.1 to Follow-up is not long enough/Data is not mature to provide upper bound 90% CI.

Adverse Events

Cohort 1: HR+/HER2-

Serious events: 22 serious events

Other events: 45 other events

Deaths: 4 deaths

Cohort 2: TNBC

Serious events: 13 serious events

Other events: 37 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Erica Mayer

Dana-Farber Cancer Institute

Phone: 617-632-2335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1: HR+/HER2- n=45 participants at risk Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.	Cohort 2: TNBC n=38 participants at risk Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Investigations Alkaline phosphatase increased	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	4.4% 2/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	0.00% 0/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	5.3% 2/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	2.6% 1/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	4.4% 2/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	5.3% 2/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Lip infection	0.00% 0/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	2.6% 1/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	0.00% 0/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	2.6% 1/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	35.6% 16/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	10.5% 4/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral motor neuropathy	6.7% 3/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	0.00% 0/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral sensory neuropathy	4.4% 2/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	5.3% 2/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Thromboembolic event	0.00% 0/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	2.6% 1/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	2.2% 1/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	5.3% 2/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	4.4% 2/45 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.	2.6% 1/38 • Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.