Trial Outcomes & Findings for Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer (NCT NCT01912963)

NCT ID: NCT01912963

Last Updated: 2018-12-05

Results Overview

The RP2D of eribulin in combination with pertuzumab and trastuzumab is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The RP2D is defined as the highest dose at which fewer than one-third of six patients experience a DLT. In this Phase I run-in, only 2 dose levels were under evaluation: a starting dose (D1) and a de-escalation dose (D-1) if 2 or more DLTs are observed in Dose Level 1 (DL1).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: The observation period for the RP2D was the 1st cycle of treatment.
• Results posted on: 2018-12-05

Participant Flow

Participants enrolled from September 2013 through May 2016.

Participant milestones

Measure	Phase I: Dose Level 1 (D1) Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort A: Without Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase. Pertuzumab Trastuzumab eribulin
Overall Study STARTED	6	19	7
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	6	19	7

Reasons for withdrawal

Measure	Phase I: Dose Level 1 (D1) Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort A: Without Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase. Pertuzumab Trastuzumab eribulin
Overall Study Disease Progression (RECIST1.1)	6	9	5
Overall Study Disease Progression (not RECIST1.1)	0	7	1
Overall Study Adverse Event	0	1	1
Overall Study Withdrawal by Subject	0	1	0
Overall Study Sought treatment locally	0	1	0

Baseline Characteristics

Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer

Baseline characteristics by cohort

Measure	Phase I: Dose Level 1 (D1) n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort A: Without Prior Pertuzumab Exposure n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase. Pertuzumab Trastuzumab eribulin	Total n=32 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	53 years n=7 Participants	47 years n=5 Participants	53 years n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	19 Participants n=7 Participants	7 Participants n=5 Participants	31 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	14 Participants n=7 Participants	7 Participants n=5 Participants	27 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	6 count of participants n=5 Participants	19 count of participants n=7 Participants	7 count of participants n=5 Participants	32 count of participants n=4 Participants
Time from Primary Diagnosis to metastatic diagnosis < 2 years	1 count of participants n=5 Participants	5 count of participants n=7 Participants	4 count of participants n=5 Participants	10 count of participants n=4 Participants
Time from Primary Diagnosis to metastatic diagnosis > 2 years	2 count of participants n=5 Participants	8 count of participants n=7 Participants	2 count of participants n=5 Participants	12 count of participants n=4 Participants
Time from Primary Diagnosis to metastatic diagnosis Metastatic diagnosis at primary diagnosis	3 count of participants n=5 Participants	6 count of participants n=7 Participants	1 count of participants n=5 Participants	10 count of participants n=4 Participants
ECOG PS ECOG PS 0	5 count of participants n=5 Participants	14 count of participants n=7 Participants	4 count of participants n=5 Participants	23 count of participants n=4 Participants
ECOG PS ECOG PS 1	1 count of participants n=5 Participants	4 count of participants n=7 Participants	3 count of participants n=5 Participants	8 count of participants n=4 Participants
ECOG PS Unknown	0 count of participants n=5 Participants	1 count of participants n=7 Participants	0 count of participants n=5 Participants	1 count of participants n=4 Participants

PRIMARY outcome

Timeframe: The observation period for the RP2D was the 1st cycle of treatment.

Population: The analysis dataset is comprised all enrolled Phase I participants.

The RP2D of eribulin in combination with pertuzumab and trastuzumab is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The RP2D is defined as the highest dose at which fewer than one-third of six patients experience a DLT. In this Phase I run-in, only 2 dose levels were under evaluation: a starting dose (D1) and a de-escalation dose (D-1) if 2 or more DLTs are observed in Dose Level 1 (DL1).

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Eribulin the Recommended Phase II Dose (RP2D) [Phase I]	1.4 mg/m^2	—

PRIMARY outcome

Timeframe: The observation period for DLTs was the 1st cycle of treatment.

A DLT was defined as an adverse event that (a) is deemed by the investigator to be probably or likely related with protocol therapy and (b) occurs during and/or begins during the first cycle of the study treatment, and (c) meets any of the following criteria: grade 4 hematologic toxicity with > 1 week of duration, grade 3 or 4 febrile neutropenia of any duration; or grade 3 or 4 non hematologic toxicity (excluding nausea, vomiting, and alopecia).

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Dose Limiting Toxicity (DLT) [Phase I]	0 Participants	—

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 2 or 3 cycles in the treatment and extension phase, respectively. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.

Population: The analysis dataset is comprised all enrolled Phase II patients.

The objective response rate (ORR) was defined as the proportion 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.

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Objective Response Rate (ORR) [Phase II]	0.26 proportion of participants Interval 0.09 to 0.51	0.0 proportion of participants Interval 0.0 to 0.41

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 2 or 3 cycles in the treatment and extension phase, respectively. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.

The clinical benefit rate (CBR) was defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer 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. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Clinical Benefit Rate (CBR) [Phase II]	.316 proportion of participants Interval 0.126 to 0.566	.143 proportion of participants Interval 0.004 to 0.579

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline, every 2 or 3 cycles in the treatment and extension phase, respectively, and every 9 weeks post-treatment until disease progression. Median follow-up in this study cohort was 15.6 months (up to 20).

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.(whichever occurs first).

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Progression-free Survival (PFS) [Phase II]	6.9 months Interval 3.5 to 11.0	3 months Interval 2.1 to The upper confidence limit was not estimable based on the Kaplan-Meier method because of insufficient follow-up.

SECONDARY outcome

Timeframe: In long-term follow-up, participants were followed for survival every 6 months up to 1 year after treatment discontinuation. Median follow-up in this study cohort was 15.6 months (up to 20).

Overall survival (OS) is defined as the time from the date of registration to the date of death, or censored at the date the participant was last known alive. OS is estimated based on the Kaplan-Meier method.

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Overall Survival (OS) [Phase II]	13.9 months Interval 11.2 to The upper confidence limit was not estimable based on the Kaplan-Meier method because of insufficient follow-up.	7.4 months Interval 5.7 to The upper confidence limit was not estimable based on the Kaplan-Meier method because of insufficient follow-up.

SECONDARY outcome

Timeframe: AEs were assessed every cycle on treatment. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.

Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) of any type during the time of observation as reported on case report forms. 'Treatment-related' is a treatment attribution of possibly, probably or definite based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Grade 4 Treatment-Related Toxicity Rate	10.5 percentage of participants Interval 1.29 to 33.1	14.3 percentage of participants Interval 0.4 to 57.9

POST_HOC outcome

Timeframe: In long-term follow-up, participants were followed for survival every 6 months up to 1 year after treatment discontinuation. Median follow-up in this study cohort was 15.6 months (up to 20).

1-year overall survival is the probability of patients remaining alive 1 year from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up.

Outcome measures

Measure	Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1 n=19 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=6 Participants Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
1-year Overall Survival	61.1 probability Interval 42.3 to 88.3	50 probability Interval 22.5 to 100.0

Adverse Events

Phase I: Dose Level 1 (D1)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II Cohort A: Without Prior Pertuzumab Exposure

Serious events: 7 serious events

Other events: 18 other events

Deaths: 0 deaths

Phase II Cohort B: With Prior Pertuzumab Exposure

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase I: Dose Level 1 (D1) n=6 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort A: Without Prior Pertuzumab Exposure n=19 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Blood and lymphatic system disorders Anemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Ataxia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophagitis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	50.0% 3/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	57.1% 4/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral motor neuropathy	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Sepsis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.

Other adverse events

Measure	Phase I: Dose Level 1 (D1) n=6 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1) Cycle duration=21 days The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort A: Without Prior Pertuzumab Exposure n=19 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.	Phase II Cohort B: With Prior Pertuzumab Exposure n=7 participants at risk Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1 Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1 Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose) Cycle duration=21 days In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	31.6% 6/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Ataxia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Bladder infection	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Bronchial infection	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Eye disorders Cataract	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Cheilitis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Chills	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	36.8% 7/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	42.9% 3/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dizziness	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Edema limbs	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophagitis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Facial nerve disorder	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	100.0% 6/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	57.1% 4/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Fever	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Flu like symptoms	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Gait disturbance	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Infusion related reaction	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Investigations - Other	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Memory impairment	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Nail discoloration	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	42.1% 8/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
General disorders Pain	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Cardiac disorders Palpitations	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Paronychia	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral motor neuropathy	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	31.6% 6/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral sensory neuropathy	33.3% 2/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	31.6% 6/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	28.6% 2/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Rash pustular	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	10.5% 2/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Sinusitis	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Skin infection	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Ear and labyrinth disorders Tinnitus	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Toothache	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Nervous system disorders Tremor	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Upper respiratory infection	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Infections and infestations Urinary tract infection	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Urinary tract pain	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	5.3% 1/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	21.1% 4/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Eye disorders Watering eyes	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	14.3% 1/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	16.7% 1/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	0.00% 0/6 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	15.8% 3/19 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.	0.00% 0/7 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.

Additional Information

Rachel Freeman MD

Dana-Farber Cancer Institute

Phone: 617.632.3000

Email: Rachel_Freedman@dfci.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place