Trial Outcomes & Findings for A Phase II Study of BVD-523 in Metastatic Uveal Melanoma (NCT NCT03417739)

Last Updated: 2024-06-25

Results Overview

Overall 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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

up to 52 weeks

Results posted on

2024-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	BVD-523 BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Study of BVD-523 in Metastatic Uveal Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BVD-523 n=13 Participants BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Age, Continuous	63.1 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants
Region of Enrollment United States	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Outcome measures

Outcome measures
Measure	BVD-523 n=13 Participants BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Overall Response Rate	0 percentage of participants Interval 0.0 to 20.5

SECONDARY outcome

Timeframe: up to 52 weeks

A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging

Outcome measures

Outcome measures
Measure	BVD-523 n=13 Participants BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Disease Control Rate	0 percentage of participants

SECONDARY outcome

Timeframe: Participant survival information will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure. Median follow-up was 6 months.

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

Outcome measures

Outcome measures
Measure	BVD-523 n=13 Participants BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Median Overall Survival	6.9 Months Interval 3.2 to 8.3

SECONDARY outcome

Timeframe: Between the dates of the start of trial treatment and first documentation of progressive disease. In the absence of documented progressive disease, follow-up will be censored at date of last disease assessment. up to 52 weeks

Time from enrollment on study until the tumor is progressing by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	BVD-523 n=13 Participants BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
Median Time to Tumor Progression	2 months Interval 1.8 to 3.6

SECONDARY outcome

Timeframe: Tumor biopsies are obtained 7-28 days prior to the first treatment and 12-16 days following the initial treatment in order to facilitate ERK signaling analysis, mutation analysis, sequencing, and cell line development.

MAPK pathway inhibition will be analyzed in pre-treatment and post-treatment samples to understand the effect of ERK inhibition by BVD-523

Outcome measures

Outcome data not reported

SECONDARY outcome

DNA sequencing will occur in tissue samples from patients treated on study to gain a better understanding of the genetic variability observed in uveal melanoma

Outcome measures

Outcome data not reported

Adverse Events

BVD-523

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BVD-523 n=13 participants at risk BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity. BVD-523: ERK1 and ERK2 inhibitor
Blood and lymphatic system disorders Anemia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Serum amylase increased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Other adverse events

Other adverse events
Measure	BVD-523 n=13 participants at risk BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity. BVD-523: ERK1 and ERK2 inhibitor
Blood and lymphatic system disorders Anemia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. 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, specify	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Lymph node pain	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Palpitations	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Supraventricular tachycardia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Blurred vision	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Eye disorders - Other, specify	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal distension	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal pain	46.2% 6/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Anal ulcer	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Ascites	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	76.9% 10/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophageal stenosis	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gingival pain	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Hemorrhoids	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	61.5% 8/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Rectal ulcer	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Stomach pain	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Chills	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Edema limbs	30.8% 4/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	53.8% 7/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fever	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Gait disturbance	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders General disorders and administration site conditions - Other, specify	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Non-cardiac chest pain	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Pain	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Urinary tract infection	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Injury, poisoning and procedural complications Bruising	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Injury, poisoning and procedural complications Fracture	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations CPK increased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Creatinine increased	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Serum amylase increased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	53.8% 7/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoalbuminemia	30.8% 4/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypocalcemia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypomagnesemia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. 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, specify	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dizziness	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dysgeusia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Tremor	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Agitation	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Confusion	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Hematuria	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Urine discoloration	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Vaginal inflammation	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pruritus	38.5% 5/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash acneiform	53.8% 7/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash maculo-papular	30.8% 4/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. 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, specify	23.1% 3/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hot flashes	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypotension	15.4% 2/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Thromboembolic event	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Vascular disorders - Other, specify	7.7% 1/13 • AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure up to one year. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Additional Information

Elizabeth Buchbinder, MD

Dana Farber Cancer Institute

Phone: 617-632-5055

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place