Trial Outcomes & Findings for Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression (NCT NCT00943670)
NCT ID: NCT00943670
Last Updated: 2013-05-27
Results Overview
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QTcF intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcF interval was subtracted from the average QTcF intervals to create a baseline-adjusted average QTcF interval.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
51 participants
Primary outcome timeframe
Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Results posted on
2013-05-27
Participant Flow
Between 14 July 2009 and 4 December 2009, 51 patients from 13 study sites in the United States were enrolled and initiated treatment in the study.
All patients enrolled in the study were initially treated with single-agent trastuzumab emtansine. Participants with early progressive disease could elect to receive pertuzumab in combination with trastuzumab emtansine.
Participant milestones
| Measure |
T-DM1 / T-DM1 + Pertuzumab
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.
|
|---|---|
|
Single-agent Trastuzumab Emtansine
STARTED
|
51
|
|
Single-agent Trastuzumab Emtansine
Treated
|
51
|
|
Single-agent Trastuzumab Emtansine
COMPLETED
|
9
|
|
Single-agent Trastuzumab Emtansine
NOT COMPLETED
|
42
|
|
Trastuzumab Emtansine + Pertuzumab
STARTED
|
20
|
|
Trastuzumab Emtansine + Pertuzumab
COMPLETED
|
2
|
|
Trastuzumab Emtansine + Pertuzumab
NOT COMPLETED
|
18
|
Reasons for withdrawal
| Measure |
T-DM1 / T-DM1 + Pertuzumab
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.
|
|---|---|
|
Single-agent Trastuzumab Emtansine
Physician Decision
|
2
|
|
Single-agent Trastuzumab Emtansine
Withdrawal by Subject
|
3
|
|
Single-agent Trastuzumab Emtansine
Systemic progression
|
15
|
|
Single-agent Trastuzumab Emtansine
Adverse Event
|
2
|
|
Single-agent Trastuzumab Emtansine
Early progressive disease
|
20
|
|
Trastuzumab Emtansine + Pertuzumab
Physician Decision
|
1
|
|
Trastuzumab Emtansine + Pertuzumab
Withdrawal by Subject
|
4
|
|
Trastuzumab Emtansine + Pertuzumab
Systemic progression
|
6
|
|
Trastuzumab Emtansine + Pertuzumab
Progression of brain metastases
|
2
|
|
Trastuzumab Emtansine + Pertuzumab
Adverse Event
|
5
|
Baseline Characteristics
Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression
Baseline characteristics by cohort
| Measure |
T-DM1 / T-DM1 + Pertuzumab
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.
|
|---|---|
|
Age Continuous
|
53.5 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
51 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-evaluable population consisted of patients who received T-DM1, had at least 1 interpretable pre-T-DM1 ECG measurement recorded on Cycle 1 Day 1, had at least 1 interpretable post-T-DM1 ECG measurement and who were not treated with medications that may have altered cardiac conduction. N indicates the ECG-evaluable population at each time point.
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QTcF intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcF interval was subtracted from the average QTcF intervals to create a baseline-adjusted average QTcF interval.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
4.7 milliseconds
Standard Deviation 9.6
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
1.2 milliseconds
Standard Deviation 8.3
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
-1.0 milliseconds
Standard Deviation 6.3
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 1, Day 8 [N=43]
|
-4.0 milliseconds
Standard Deviation 13.4
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
-0.1 milliseconds
Standard Deviation 10.1
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval
Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
4.7 milliseconds
Standard Deviation 10.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-Evaluable population; N indicates the ECG-evaluable population with available data at each time point.
The corrected QT interval was calculated using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTcB intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcB interval was subtracted from the average QTcB intervals to create a baseline-adjusted average QTcB interval.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
7.3 milliseconds
Standard Deviation 12.2
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
3.6 milliseconds
Standard Deviation 9.1
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
2.6 milliseconds
Standard Deviation 7.4
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 1, Day 8 [N=43]
|
0.7 milliseconds
Standard Deviation 13.1
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
3.7 milliseconds
Standard Deviation 14.5
|
—
|
—
|
—
|
|
Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction
Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
6.0 milliseconds
Standard Deviation 13.2
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-Evaluable population; N indicates the ECG-evaluable population with available data at each time point.
The uncorrected QT interval was calculated from electrocardiogram (ECG) data. Each participant had triplicate QT intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QT interval was subtracted from the average QT intervals to create a baseline-adjusted average QT interval.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in Uncorrected QT Interval
Cycle 1 Day 1, 15 minutes post-dose [N=44]
|
-2.6 milliseconds
Standard Deviation 17.4
|
—
|
—
|
—
|
|
Change From Baseline in Uncorrected QT Interval
Cycle 1 Day 1, 60 minutes post-dose [N=45]
|
-7.0 milliseconds
Standard Deviation 14.9
|
—
|
—
|
—
|
|
Change From Baseline in Uncorrected QT Interval
Cycle 1 Day 8 [N=43]
|
12.2 milliseconds
Standard Deviation 22.1
|
—
|
—
|
—
|
|
Change From Baseline in Uncorrected QT Interval
Cycle 3 Day 1, 15 minutes pre-dose [N=35]
|
-7.0 milliseconds
Standard Deviation 14.9
|
—
|
—
|
—
|
|
Change From Baseline in Uncorrected QT Interval
Cycle 3 Day 1, 15 minutes post-dose [N=37]
|
2.4 milliseconds
Standard Deviation 16.4
|
—
|
—
|
—
|
|
Change From Baseline in Uncorrected QT Interval
Cycle 3 Day 1, 60 minutes post-dose [N=37]
|
0.1 milliseconds
Standard Deviation 19.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-Evaluable population
The PR interval is the time in seconds from the beginning of the P wave to the beginning of the QRS complex, and was calculated from electrocardiogram (ECG) data. Each participant had triplicate PR intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline PR interval was subtracted from the average PR intervals to create a baseline-adjusted average PR interval.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in PR Interval
Cycle 1 Day 1, 15 minutes post-dose [N=44]
|
2.3 milliseconds
Standard Deviation 7.5
|
—
|
—
|
—
|
|
Change From Baseline in PR Interval
Cycle 1 Day 1, 60 minutes post-dose [N=45]
|
2.5 milliseconds
Standard Deviation 8.7
|
—
|
—
|
—
|
|
Change From Baseline in PR Interval
Cycle 1 Day 8 [N=43]
|
-0.7 milliseconds
Standard Deviation 10.7
|
—
|
—
|
—
|
|
Change From Baseline in PR Interval
Cycle 3 Day 1, 15 minutes pre-dose [N=35]
|
1.8 milliseconds
Standard Deviation 11.0
|
—
|
—
|
—
|
|
Change From Baseline in PR Interval
Cycle 3 Day 1, 15 minutes post-dose [N=37]
|
6.7 milliseconds
Standard Deviation 9.8
|
—
|
—
|
—
|
|
Change From Baseline in PR Interval
Cycle 3 Day 1, 60 minutes post-dose [N=37]
|
5.3 milliseconds
Standard Deviation 8.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-Evaluable population; N indicates the ECG-evaluable population with available data at each time point.
The QRS interval represents the time it takes for depolarization of the ventricles and was calculated from electrocardiogram (ECG) data. Each participant had triplicate QRS intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QRS interval was subtracted from the average QRS intervals to create a baseline-adjusted average QRS interval.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in QRS Duration
Cycle 1 Day 1, 15 minutes post-dose [N=44]
|
1.2 milliseconds
Standard Deviation 3.1
|
—
|
—
|
—
|
|
Change From Baseline in QRS Duration
Cycle 1 Day 1, 60 minutes post-dose [N=45]
|
0.4 milliseconds
Standard Deviation 3.0
|
—
|
—
|
—
|
|
Change From Baseline in QRS Duration
Cycle 1 Day 8 [N=43]
|
1.1 milliseconds
Standard Deviation 4.8
|
—
|
—
|
—
|
|
Change From Baseline in QRS Duration
Cycle 3 Day 1, 15 minutes pre-dose [N=35]
|
0.5 milliseconds
Standard Deviation 4.5
|
—
|
—
|
—
|
|
Change From Baseline in QRS Duration
Cycle 3 Day 1, 15 minutes post-dose [N=37]
|
1.9 milliseconds
Standard Deviation 4.0
|
—
|
—
|
—
|
|
Change From Baseline in QRS Duration
Cycle 3 Day 1, 60 minutes post-dose [N=37]
|
1.5 milliseconds
Standard Deviation 3.8
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-evaluable population; N indicates the ECG-evaluable population with available data at each time point.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Change From Baseline in Heart Rate
Cycle 1 Day 1, 15 minutes post-dose [N=44]
|
2.9 beats per minute
Standard Deviation 8.3
|
—
|
—
|
—
|
|
Change From Baseline in Heart Rate
Cycle 1 Day 1, 60 minutes post-dose [N=45]
|
4.4 beats per minute
Standard Deviation 7.9
|
—
|
—
|
—
|
|
Change From Baseline in Heart Rate
Cycle 1 Day 8 [N=43]
|
5.4 beats per minute
Standard Deviation 8.8
|
—
|
—
|
—
|
|
Change From Baseline in Heart Rate
Cycle 3 Day 1, 15 minutes pre-dose [N=35]
|
4.1 beats per minute
Standard Deviation 7.9
|
—
|
—
|
—
|
|
Change From Baseline in Heart Rate
Cycle 3 Day 1, 15 minutes post-dose [N=37]
|
0.8 beats per minute
Standard Deviation 7.6
|
—
|
—
|
—
|
|
Change From Baseline in Heart Rate
Cycle 3 Day 1, 60 minutes post-dose [N=37]
|
2.4 beats per minute
Standard Deviation 7.8
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: The number of participants analyzed for each QTc interval category represents the total treated population. N indicates the ECG-evaluable population with available data at each time point.
The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
n=51 Participants
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
n=51 Participants
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
n=51 Participants
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
97.3 percentage of participants
|
2.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
73.3 percentage of participants
|
26.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
70.3 percentage of participants
|
29.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 1, Day 8 [N=43]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
97.1 percentage of participants
|
2.9 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcF: Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
94.6 percentage of participants
|
5.4 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
79.5 percentage of participants
|
20.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 1, Day 8 [N=43]
|
79.1 percentage of participants
|
20.9 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
82.9 percentage of participants
|
17.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Within Each Absolute QTc Interval Category
QTcB: Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
70.3 percentage of participants
|
29.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: The number of participants analyzed for each QTc interval category represents the total treated population. N indicates the ECG-evaluable population with available data at each time point.
The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTc interval was subtracted from the average QTc intervals to create a baseline-adjusted average QTc interval. QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
n=51 Participants
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
n=51 Participants
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 1, Day 8 [N=43]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
97.3 percentage of participants
|
2.7 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 1, Day 8 [N=43]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
94.3 percentage of participants
|
5.7 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcB: Cycle 3, Day 1, 15 minutes post-dose [N=37]
|
94.6 percentage of participants
|
5.4 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
|
Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
QTcF: Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
100 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-evaluable population; N indicates the ECG-evaluable population with available data at each time point.
The incidence of abnormal U-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants With New Abnormal U Waves
Cycle 1, Day 1, 15 minutes post-dose [N=44]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal U Waves
Cycle 1, Day 1, 60 minutes post-dose [N=45]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal U Waves
Cycle 1, Day 8 [N=43]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal U Waves
Cycle 3, Day 1, 15 minutes pre-dose [N=35]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal U Waves
Cycle 3, Day 1, 15 minutes post-dose [N=36]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal U Waves
Cycle 3, Day 1, 60 minutes post-dose [N=37]
|
0 percentage of participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.Population: ECG-Evaluable population; N indicates the ECG-evaluable population with available data at each time point.
The incidence of abnormal T-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. C=Cycle; D=Day.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants With New Abnormal T Waves
Significant: C1D1, 15 minutes post-dose [N=44]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Significant: C1D1, 60 minutes post-dose [N=45]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Significant: C1D8 [N=43]
|
2.3 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Significant: C3D1, 15 minutes pre-dose [N=35]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Significant: C3D1, 15 minutes post-dose [N=36]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Significant: C3D1, 60 minutes post-dose [N=37]
|
0 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C1D1, 15 minutes post-dose [N=44]
|
13.6 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C1D1, 60 minutes post-dose [N=45]
|
11.1 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C1D8 [N=43]
|
20.9 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C3D1, 15 minutes pre-dose [N=35]
|
17.1 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C3D1, 15 minutes post-dose [N=36]
|
13.9 percentage of participants
|
—
|
—
|
—
|
|
Percentage of Participants With New Abnormal T Waves
Non-Significant: C3D1, 60 minutes post-dose [N=37]
|
27.0 percentage of participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).Population: The efficacy-evaluable population was defined as patients who received at least one dose of study drug. Patients with missing or no post-baseline response assessments were classified as non-responders.
Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments conducted by the investigator ≥ 4 weeks apart. Responses were assessed by physical examination and imaged-based evaluation using a modified version of the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0: CR-the disappearance of all target lesions and the disappearance of all nontarget lesions and normalization of tumor marker level and no new lesions. PR-either the disappearance of all target lesions with persistence of one or more nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter with no new lesions or unequivocal progression of existing nontarget lesions.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants With an Objective Response During the Single-agent Trastuzumab Emtansine Treatment Period
|
25.5 percentage of participants
Interval 15.2 to 38.5
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Time from the first documented objective response to the time of first documented disease progression or death, up to a maximum time period of one year.Population: Efficacy evaluable patients who achieved an objective response.
In patients with an objective response during the single-agent trastuzumab emtansine treatment period, duration of response was defined as the time from the first documented objective response to the time of first documented disease progression or death, whichever occurred first. Progressive disease was defined as either at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study with an absolute increase of at least 5 mm, or the appearance of one or more new lesions, or the unequivocal progression of existing nontarget lesions. If a patient did not die or experience disease progression before the end of the study, duration of response was censored at the day of the last tumor assessment when the patient was known to be progression free.
Outcome measures
| Measure |
T-DM1
n=13 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Duration of Objective Response Based on Investigator Assessment During the Single-agent Trastuzumab Emtansine Treatment Period
|
9.3 months
Interval 4.7 to
Upper limit of the confidence not estimable due to the low number of patients with an event (7).
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From the first day of study treatment to the first documented disease progression or death, up to a maximum time period of one year.Population: Efficacy evaluable patients.
Progression-free survival (PFS) was defined as the time from the first day of study treatment (Day 1) to first documented disease progression or death, whichever occurred first. If a patient did not experience disease progression or die, PFS was censored at the day of the last tumor assessment that a patient was known to be progression free.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Progression-free Survival During the Single-agent Trastuzumab Emtansine Treatment Period
|
4.3 months
Interval 4.0 to 6.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).Population: The efficacy-evaluable population was defined as patients who received at least one dose of study drug.
Participants were considered to have experienced clinical benefit if they had an objective response or maintained stable disease for at least 6 months from start of study treatment. Objective response was defined as a complete or partial response determined on two consecutive tumor assessments at least 4 weeks apart based on a modified version of RECIST. Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started and no new lesions or unequivocal progression of existing nontarget lesions.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Percentage of Participants With Clinical Benefit During the Single-agent Trastuzumab Emtansine Treatment Period
|
39.2 percentage of participants
Interval 25.8 to 53.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose until 30 days after last dose (up to 1 year).Population: Safety-Evaluable Patients (i.e., the treated population).
An serious AE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s), or is considered a significant medical event by the investigator (e.g., may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above). The severity of each AE was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0, or as follows: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Very severe; Grade 5 = Death related to AE.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
n=20 Participants
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Adverse events leading to treatment discontinuatio
|
2 participants
|
5 participants
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs)
Any adverse event
|
51 participants
|
18 participants
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs)
Grade ≥ 3 adverse events
|
17 participants
|
12 participants
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs)
Serious adverse events
|
4 participants
|
5 participants
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs)
Deaths
|
0 participants
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Assessed at Baseline and after every 3 cycles, up to 1 year.Population: Safety-Evaluable Patients (i.e., the treated population).
Left ventricular ejection fraction (LVEF) was assessed on the basis of local assessments of echocardiogram or multigated acquisition scan (MUGA) data. A decrease in LVEF is defined as a decrease from Baseline of greater than or equal to 15%. Grade 3 LVEF is an ejection fraction between 20 and 40%.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
n=20 Participants
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Number of Participants With Decreased Ejection Fraction
Grade 3
|
1 participants
|
0 participants
|
—
|
—
|
|
Number of Participants With Decreased Ejection Fraction
Overall
|
1 participants
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: Pharmacokinetic (PK)-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Serum samples were quantitated for T-DM1 (DM1 conjugated to trastuzumab) levels in a validated assay using an indirect sandwich enzyme-linked immunosorbent assay (ELISA). The minimum quantifiable concentration in human serum was 40 ng/mL. Serum samples were assayed for total trastuzumab (conjugated and unconjugated T-DM1) in a validated assay using an indirect sandwich ELISA method; the minimum quantifiable concentration in human serum was 40 ng/mL.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab
Cycle 1: T-DM1 [N=51]
|
75.6 μg/mL
Standard Deviation 21.9
|
—
|
—
|
—
|
|
Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab
Cycle 1: Total trastuzumab [N=51]
|
95.9 μg/mL
Standard Deviation 32.3
|
—
|
—
|
—
|
|
Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab
Cycle 3: T-Dm1 [N=47]
|
80.7 μg/mL
Standard Deviation 18.1
|
—
|
—
|
—
|
|
Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab
Cycle 3: Total trastuzumab [N=47]
|
98.6 μg/mL
Standard Deviation 26.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: PK-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Area under the serum concentration-time curve from Time zero to time of last measurable concentration (AUClast) for T-DM1 (conjugated trastuzumab) and Total Trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1 and Cycle 3.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab
Cycle 1: T-DM1 [N=51]
|
418 μg * day/mL
Standard Deviation 121
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab
Cycle 1: Total trastuzumab [N=51]
|
929 μg * day/mL
Standard Deviation 564
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab
Cycle 3: T-Dm1 [N=47]
|
475 μg * day/mL
Standard Deviation 150
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab
Cycle 3: Total trastuzumab [N=47]
|
958 μg * day/mL
Standard Deviation 394
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycle 1.Population: PK-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Area under the serum concentration-time curve from Time zero extrapolated to infinity (AUCinf) for T-DM1 (conjugated trastuzumab) and total trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity for T-DM1 and Total Trastuzumab
T-DM1
|
431 μg * day/mL
Standard Deviation 126
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity for T-DM1 and Total Trastuzumab
Total trastuzumab
|
1420 μg * day/mL
Standard Deviation 1390
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: PK-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Terminal Half-life for T-DM1 and Total Trastuzumab
Cycle 1: T-DM1 [N=51]
|
4.02 days
Standard Deviation 0.938
|
—
|
—
|
—
|
|
Terminal Half-life for T-DM1 and Total Trastuzumab
Cycle 1: Total trastuzumab [N=51]
|
10.3 days
Standard Deviation 6.81
|
—
|
—
|
—
|
|
Terminal Half-life for T-DM1 and Total Trastuzumab
Cycle 3: T-Dm1 [N=47]
|
4.46 days
Standard Deviation 0.926
|
—
|
—
|
—
|
|
Terminal Half-life for T-DM1 and Total Trastuzumab
Cycle 3: Total trastuzumab [N=47]
|
12.0 days
Standard Deviation 6.24
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: PK-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Clearance T-DM1 and Total Trastuzumab
Cycle 1: T-DM1 [N=51]
|
9.17 mL/day/kg
Standard Deviation 3.03
|
—
|
—
|
—
|
|
Clearance T-DM1 and Total Trastuzumab
Cycle 1: Total trastuzumab [N=51]
|
4.21 mL/day/kg
Standard Deviation 2.43
|
—
|
—
|
—
|
|
Clearance T-DM1 and Total Trastuzumab
Cycle 3: T-Dm1 [N=47]
|
7.91 mL/day/kg
Standard Deviation 3.30
|
—
|
—
|
—
|
|
Clearance T-DM1 and Total Trastuzumab
Cycle 3: Total trastuzumab [N=47]
|
3.12 mL/day/kg
Standard Deviation 1.71
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: PK-evaluable patients were defined as patients who had adequate concentration-time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Outcome measures
| Measure |
T-DM1
n=51 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab
Cycle 1: T-DM1 [N=51]
|
41.2 mL/kg
Standard Deviation 24.5
|
—
|
—
|
—
|
|
Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab
Cycle 1: Total trastuzumab [N=51]
|
41.9 mL/kg
Standard Deviation 16.2
|
—
|
—
|
—
|
|
Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab
Cycle 3: T-Dm1 [N=47]
|
43.6 mL/kg
Standard Deviation 40.7
|
—
|
—
|
—
|
|
Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab
Cycle 3: Total trastuzumab [N=47]
|
43.7 mL/kg
Standard Deviation 15.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.Population: Evaluable patients, defined as patients who had at least one ATA measurement available for analysis at Baseline (pre-dose in Cycle 1) and post-baseline.
The number of participants with anti-T-DM1 antibodies was assessed using a validated bridging antibody enzyme-linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
T-DM1
n=47 Participants
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 450 to ≤ 480 ms
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 480 to ≤ 500 ms
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
Average QTc Interval > 500 ms
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
|---|---|---|---|---|
|
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Trastuzumab Emtansine
Pre-dose (Baseline)
|
2 participants
|
—
|
—
|
—
|
|
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Trastuzumab Emtansine
Post-dose
|
0 participants
|
—
|
—
|
—
|
Adverse Events
Single-Agent T-DM1 Treatment
Serious events: 4 serious events
Other events: 51 other events
Deaths: 0 deaths
T-DM1 + Pertuzumab
Serious events: 5 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Single-Agent T-DM1 Treatment
n=51 participants at risk
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
T-DM1 + Pertuzumab
n=20 participants at risk
Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Generalised oedema
|
2.0%
1/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Convulsion
|
2.0%
1/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Renal and urinary disorders
Renal failure
|
2.0%
1/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
1/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
Other adverse events
| Measure |
Single-Agent T-DM1 Treatment
n=51 participants at risk
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
|
T-DM1 + Pertuzumab
n=20 participants at risk
Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.7%
7/51 • 1 year
|
30.0%
6/20 • 1 year
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
33.3%
17/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Cardiac disorders
Cardiac flutter
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Cardiac disorders
Tachycardia
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Eye disorders
Diplopia
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Eye disorders
Vision blurred
|
11.8%
6/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
31.4%
16/51 • 1 year
|
20.0%
4/20 • 1 year
|
|
Gastrointestinal disorders
Diarrhoea
|
7.8%
4/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
64.7%
33/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
7.8%
4/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
49.0%
25/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Gastrointestinal disorders
Abdominal distension
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
23.5%
12/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Dysphagia
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Faecal incontinence
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Gastritis
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Stomatitis
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
General disorders
Fatigue
|
64.7%
33/51 • 1 year
|
20.0%
4/20 • 1 year
|
|
General disorders
Pain
|
7.8%
4/51 • 1 year
|
20.0%
4/20 • 1 year
|
|
General disorders
Pyrexia
|
23.5%
12/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
General disorders
Catheter site erythema
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Chest discomfort
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Chest pain
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Drug effect increased
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Medical device complication
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Oedema peripheral
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Thirst
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
General disorders
Chills
|
21.6%
11/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
General disorders
Asthenia
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
General disorders
Gait disturbance
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Hepatobiliary disorders
Biliary dilatation
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Infections and infestations
Upper respiratory tract infection
|
17.6%
9/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Infections and infestations
Catheter site cellulitis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Infections and infestations
Cellulitis
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Infections and infestations
Conjunctivitis infective
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Infections and infestations
Device related infection
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
17.6%
9/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Infections and infestations
Herpes zoster
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Injury, poisoning and procedural complications
Gastroenteritis radiation
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
17/51 • 1 year
|
20.0%
4/20 • 1 year
|
|
Investigations
Blood alkaline phosphatase increased
|
7.8%
4/51 • 1 year
|
20.0%
4/20 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
13.7%
7/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Investigations
Weight decreased
|
9.8%
5/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Investigations
Ejection fraction decreased
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Investigations
Haemoglobin decreased
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Investigations
International normalised ratio increased
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Investigations
Weight increased
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Investigations
Blood lactate dehydrogenase increased
|
15.7%
8/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Metabolism and nutrition disorders
Decreased appetite
|
23.5%
12/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
23.5%
12/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
9.8%
5/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
3.9%
2/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.8%
4/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.0%
1/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.8%
6/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.6%
9/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.8%
4/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
3.9%
2/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.8%
5/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Dizziness
|
9.8%
5/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Nervous system disorders
Headache
|
21.6%
11/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Nervous system disorders
Ataxia
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Central nervous system lesion
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Facial paresis
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Memory impairment
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Migraine
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Neuropathy peripheral
|
11.8%
6/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Restless legs syndrome
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Sedation
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
11.8%
6/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Nervous system disorders
Paraesthesia
|
9.8%
5/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Nervous system disorders
Hypoaesthesia
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Psychiatric disorders
Depression
|
5.9%
3/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Psychiatric disorders
Anxiety
|
5.9%
3/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Psychiatric disorders
Insomnia
|
15.7%
8/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Psychiatric disorders
Food aversion
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Renal and urinary disorders
Micturition disorder
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Renal and urinary disorders
Proteinuria
|
11.8%
6/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
5.9%
3/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.6%
10/51 • 1 year
|
15.0%
3/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.7%
8/51 • 1 year
|
10.0%
2/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.7%
7/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.8%
4/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Papule
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.8%
5/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Subcutaneous nodule
|
0.00%
0/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Blister
|
7.8%
4/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
5.9%
3/51 • 1 year
|
0.00%
0/20 • 1 year
|
|
Vascular disorders
Flushing
|
2.0%
1/51 • 1 year
|
5.0%
1/20 • 1 year
|
|
Vascular disorders
Hypertension
|
13.7%
7/51 • 1 year
|
0.00%
0/20 • 1 year
|
Additional Information
Medical Communications
Hoffman-LaRoche
Phone: 800-821-8590
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER