Trial Outcomes & Findings for MSC2015103B in Solid Tumors (NCT NCT01453387)

Last Updated: 2017-05-08

Results Overview

DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Up to Day 21 of Cycle 1

Results posted on

2017-05-08

Participant Flow

First/Last subject (informed consent): 09 September 2011/18 April 2013. Study completion date: 15 July 2013, Clinical data cut-off date: 15 July 2013; Subjects were randomized at 3 centers in United States.

Enrolled: 28 subjects were screened for eligibility and all were randomized in to the trial.

Participant milestones

Participant milestones
Measure	Part 1 - MSC2015103B (Schedule 1) MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.
Overall Study STARTED	21	7
Overall Study COMPLETED	21	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

MSC2015103B in Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Total n=28 Participants Total of all reporting groups
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	3 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized 18 to less than (<) 45 years	2 Subjects n=5 Participants	0 Subjects n=7 Participants	2 Subjects n=5 Participants
Age, Customized Greater than equal to (>=) 45 to <65 years	10 Subjects n=5 Participants	5 Subjects n=7 Participants	15 Subjects n=5 Participants
Age, Customized >=65 years	9 Subjects n=5 Participants	2 Subjects n=7 Participants	11 Subjects n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 21 of Cycle 1

Population: Safety analysis set included all the subjects who received at least one administration of the trial medication.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Number of Subjects Who Experienced Dose-limiting Toxicities (DLT)	0 Subjects	0 Subjects	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 21 of Cycle 1

Population: Safety analysis set included all subjects who received at least one administration of the trial medication.

DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Percentage of Subjects Who Experienced DLT	0 Percentage of subjects	0 Percentage of subjects	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the initiation of the trial till the data cut-off date 15 July 2013

Population: The safety analysis set included all the subjects who received at least one administration of the trial medication.

An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE (Serious adverse event) is defined as any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.. TEAEs are events between first dose of study drug up to the cut-off date (15 July 2013) and were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation TEAEs	100.0 Percentage of subjects	100.0 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation Serious TEAEs	19.0 Percentage of subjects	42.9 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation TEAEs leading to death	0.0 Percentage of subjects	0.0 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation TEAEs leading to discontinuation	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the initiation of the trial till the data cut-off date 15 July 2013

Population: The safety analysis set included all the subjects who received at least one administration of the trial medication.

Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Aspartate aminotransferase increased	14.3 Percentage of subjects	0.0 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Decreased appetite	14.3 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Gamma-glutamyl transferase increased	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Blood alkaline phosphatase increased	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Ejection fraction decreased	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Blood glucose increased	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypokalemia	0.0 Percentage of subjects	28.6 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hyponatraemia	0.0 Percentage of subjects	28.6 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypoalbuminaemia	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypophosphatemia	0.0 Percentage of subjects	14.3 Percentage of subjects	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the initiation of the trial till the data cut-off date 15 July 2013

Population: The safety analysis set included all the subjects who received at least one administration of the trial medication.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Aspartate aminotransferase increased	3 Subjects	0 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Decreased appetite	3 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Gamma-glutamyl transferase increased	0 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Blood alkaline phosphatase increased	0 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Ejection fraction decreased	0 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Blood glucose increased	0 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypokalemia	0 Subjects	2 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hyponatraemia	0 Subjects	2 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypoalbuminaemia	0 Subjects	1 Subjects	—	—	—	—	—	—	—
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication Hypophosphatemia	0 Subjects	1 Subjects	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Schedule 1 : 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Days 1 and 17.

Population: Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Maximum Plasma Concentration (Cmax) Week 1 (n=3, 4, 3, 3, 3, 3, 2, 3, 4)	38.750 Picogram per milliliter Interval 25.2 to 58.9	38.110 Picogram per milliliter Interval 25.4 to 56.7	97.293 Picogram per milliliter Interval 34.4 to 179.2	290.98 Picogram per milliliter Interval 199.1 to 441.0	396.45 Picogram per milliliter Interval 193.7 to 657.2	888.15 Picogram per milliliter Interval 295.0 to 3010.0	2215.9 Picogram per milliliter Interval 1760.0 to 2790.0	75.313 Picogram per milliliter Interval 55.6 to 98.5	52.331 Picogram per milliliter Interval 33.4 to 72.7
Maximum Plasma Concentration (Cmax) Week 2 (n= 3,3,3,3,1,3,2,2,3)	48.952 Picogram per milliliter Interval 29.7 to 82.8	63.732 Picogram per milliliter Interval 54.5 to 74.8	219.71 Picogram per milliliter Interval 108.1 to 336.1	329.62 Picogram per milliliter Interval 257.3 to 439.5	2471.0 Picogram per milliliter Interval 2471.0 to 2471.0	1728.1 Picogram per milliliter Interval 835.0 to 2630.0	5636.8 Picogram per milliliter Interval 5340.0 to 5950.0	190.59 Picogram per milliliter Interval 141.4 to 256.9	157.62 Picogram per milliliter Interval 80.1 to 404.0

SECONDARY outcome

Timeframe: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Time to Reach Maximum Plasma Concentration (Tmax) Week 1 (n=3,4,3,3,3,3,2,3,4)	2.4478 Hour Interval 1.833 to 4.0	5.2643 Hour Interval 4.0 to 8.0	1.4422 Hour Interval 1.0 to 2.0	1.4422 Hour Interval 1.0 to 2.0	1.5874 Hour Interval 1.0 to 4.0	1.1447 Hour Interval 0.5 to 2.0	1.2450 Hour Interval 1.033 to 1.5	2.4248 Hour Interval 1.5 to 6.067	1.3161 Hour Interval 1.0 to 2.0
Time to Reach Maximum Plasma Concentration (Tmax) Week 3 (n=3,3,3,3,1,3,2,2,3)	1.1573 Hour Interval 1.0 to 1.5	2.3833 Hour Interval 1.5 to 6.017	4.5789 Hour Interval 2.0 to 8.0	1.1635 Hour Interval 1.0 to 1.5	0.50000 Hour Interval 0.5 to 0.5	2.0110 Hour Interval 1.017 to 4.0	0.70711 Hour Interval 0.5 to 1.0	2.8519 Hour Interval 2.033 to 4.0	1.6869 Hour Interval 1.5 to 2.133

SECONDARY outcome

Timeframe: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.

Population: Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose."n" signifies the number of subjects evaluable for the particular timepoint.

The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Apparent Terminal Half Life (T1/2) Week 1 (n=3,4,3,3,3,3,2,3,4)	134.88 Hour Interval 72.76 to 201.9	115.41 Hour Interval 73.51 to 280.2	55.023 Hour Interval 20.85 to 118.7	53.072 Hour Interval 51.51 to 55.1	115.34 Hour Interval 85.23 to 135.4	52.852 Hour Interval 49.4 to 58.26	81.124 Hour Interval 33.51 to 196.4	30.850 Hour Interval 23.55 to 40.09	33.007 Hour Interval 22.74 to 46.98
Apparent Terminal Half Life (T1/2) Week 3 (n=3,3,3,3,1,3,2,2,3)	102.30 Hour Interval 41.27 to 251.3	102.53 Hour Interval 76.49 to 122.5	138.47 Hour Interval 115.5 to 191.1	55.43 Hour Interval 42.21 to 85.54	37.16 Hour Interval 37.16 to 37.16	103.77 Hour Interval 55.95 to 185.7	100.91 Hour Interval 91.41 to 111.4	121.58 Hour Interval 49.19 to 300.5	145.70 Hour Interval 56.03 to 643.5

SECONDARY outcome

Timeframe: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.

Population: Pharmacokinetic analysis set included all the subjects who have received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint.

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-inf]) Week 1 (n=3,4,3,3,3,3,2,3,4)	3644.7 Hour*picogram/milliliter Interval 1997.0 to 6477.0	3927.4 Hour*picogram/milliliter Interval 2513.0 to 5479.0	2249.9 Hour*picogram/milliliter Interval 829.0 to 4037.0	7890.1 Hour*picogram/milliliter Interval 6454.0 to 10920.0	12454 Hour*picogram/milliliter Interval 8921.0 to 23730.0	13164 Hour*picogram/milliliter Interval 6049.0 to 19880.0	23558 Hour*picogram/milliliter Interval 18580.0 to 29870.0	2032.2 Hour*picogram/milliliter Interval 1408.0 to 3234.0	1375.2 Hour*picogram/milliliter Interval 948.0 to 2377.0
Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-inf]) Week 3 (n=,3,3,3,3,1,3,2,2,3)	4715.2 Hour*picogram/milliliter Interval 1710.0 to 17490.0	4377.2 Hour*picogram/milliliter Interval 3552.0 to 6006.0	16465 Hour*picogram/milliliter Interval 7797.0 to 38300.0	12397 Hour*picogram/milliliter Interval 7532.0 to 16750.0	24580 Hour*picogram/milliliter Interval 24580.0 to 24580.0	35423 Hour*picogram/milliliter Interval 14410.0 to 68400.0	66081 Hour*picogram/milliliter Interval 61480.0 to 71020.0	21735 Hour*picogram/milliliter Interval 6093.0 to 77530.0	14870 Hour*picogram/milliliter Interval 7409.0 to 27350.0

SECONDARY outcome

Timeframe: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
AUC Versus Time Curve Within One Dosing Interval (AUC0-tau) Week 3 (n=3,3,3,3,1,3,2,2,3)	2946.9 hours*picogram/milliliter Interval 1645.0 to 6147.0	3002.0 hours*picogram/milliliter Interval 2525.0 to 3810.0	8865.3 hours*picogram/milliliter Interval 4920.0 to 16490.0	10696 hours*picogram/milliliter Interval 7208.0 to 15580.0	23670 hours*picogram/milliliter Interval 23670.0 to 23670.0	25150 hours*picogram/milliliter Interval 12190.0 to 40520.0	47114 hours*picogram/milliliter Interval 44670.0 to 49690.0	4993.3 hours*picogram/milliliter Interval 2984.0 to 8356.0	3070.5 hours*picogram/milliliter Interval 1661.0 to 7338.0
AUC Versus Time Curve Within One Dosing Interval (AUC0-tau) Week 1 (n=3,4,3,3,3,3,2,3,4)	2072.8 hours*picogram/milliliter Interval 1549.0 to 2789.0	2381.6 hours*picogram/milliliter Interval 1947.0 to 3892.0	1752.7 hours*picogram/milliliter Interval 725.1 to 3202.0	6824.4 hours*picogram/milliliter Interval 5577.0 to 9363.0	8434.6 hours*picogram/milliliter Interval 6120.0 to 13990.0	11533 hours*picogram/milliliter Interval 5498.0 to 17850.0	17698 hours*picogram/milliliter Interval 16630.0 to 18830.0	1345.3 hours*picogram/milliliter Interval 1073.0 to 1809.0	865.76 hours*picogram/milliliter Interval 738.5 to 1231.0

SECONDARY outcome

Timeframe: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1.

Population: Pharmacokinetic analysis set included all the subjects who have received at least one dose of MSC2015103B and who have provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "N" signifies the total number of subjects evaluable for this outcome measure.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Apparent Oral Clearance of the Drug From Plasma (CL/f)	41.156 Liter/hour Interval 23.16 to 75.11	50.924 Liter/hour Interval 36.51 to 79.57	133.34 Liter/hour Interval 74.3 to 361.9	57.033 Liter/hour Interval 41.19 to 69.73	52.192 Liter/hour Interval 27.39 to 72.86	75.968 Liter/hour Interval 50.29 to 165.3	63.673 Liter/hour Interval 50.22 to 80.73	73.813 Liter/hour Interval 46.38 to 106.6	145.44 Liter/hour Interval 84.15 to 211.0

SECONDARY outcome

Population: Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and who provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=3 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=4 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) n=3 Participants MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) n=3 Participants MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) n=3 Participants MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) n=3 Participants MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) n=2 Participants MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) n=3 Participants MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) n=4 Participants MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Apparent Volume of Distribution Associated to the Terminal Phase (Vz/f)	8008.6 Liter Interval 6746.0 to 9658.0	8478.7 Liter Interval 4275.0 to 14760.0	10584 Liter Interval 7219.0 to 15090.0	4366.9 Liter Interval 3275.0 to 5298.0	8684.7 Liter Interval 5349.0 to 13670.0	5792.4 Liter Interval 3722.0 to 11780.0	7452.2 Liter Interval 3903.0 to 14230.0	3285.2 Liter Interval 2682.0 to 3651.0	6925.6 Liter Interval 5704.0 to 8253.0

SECONDARY outcome

Timeframe: Schedule 1: Day 1: Pre-dose; Post-dose: 2, 4, 8, 24 hour; 48 or 72 hour; 48 or 96 hour, 168 hour; Day 15: Pre-dose; Schedule 2: Day 1: Pre-dose; Post-dose: 2, 8, 24, 48, 96 hour; Day 15: Pre-dose; Day 17: Pre-dose; Post-dose: 2, 8, and 24 hour

Population: As the trial was terminated early due to administrative reason, it was decided as per Statistical Analysis Plan not to evaluate the biomarker data for this study.

ERK phosphorylation levels were to be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 Weeks until complete response or till data cut-off date 15 July 2013

Population: The efficacy analysis set included all subjects who received at least 1(non-zero) dose of MSC2015103B and had a baseline tumor assessment.

Overall response was to be confirmed by complete response (CR) or partial response (PR) using response evaluation criteria in solid tumours Version 1.0 (RECIST) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Percentage of Subjects With Overall Response CR	0 percentage of subjects	0 percentage of subjects	—	—	—	—	—	—	—
Percentage of Subjects With Overall Response PR	0 percentage of subjects	0 percentage of subjects	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Every 6 Weeks until complete response or till data cut-off date 15 July 2013

Population: The efficacy analysis set included all subjects who received at least 1(non-zero) dose of MSC2015103B and had a baseline tumor assessment.

Clinical benefit was to be confirmed by CR, PR or stable disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.

Outcome measures

Outcome measures
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 Participants MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 Participants MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.	Part 1 - MSC2015103B 300 mcg (Schedule 1) MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 450 mcg (Schedule 1) MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 650 mcg (Schedule 1) MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1000 mcg (Schedule 1) MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 1500 mcg (Schedule 1) MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle.	Part 1 - MSC2015103B 150 mcg (Schedule 2) MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.	Part 1 - MSC2015103B 200 mcg (Schedule 2) MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle.
Percentage of Subjects With Clinical Benefit	33.3 percentage of subjects	28.6 percentage of subjects	—	—	—	—	—	—	—

Adverse Events

Part 1 - MSC2015103B (Schedule 1)

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Part 1 - MSC2015103B (Schedule 2)

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1 - MSC2015103B (Schedule 1) n=21 participants at risk MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.	Part 1 - MSC2015103B (Schedule 2) n=7 participants at risk MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently.
Gastrointestinal disorders Abdominal pain	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Gastrointestinal disorders Nausea	0.00% 0/21 • From the initiation of the trial till data cut-off date (15 July 2013)	14.3% 1/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Gastrointestinal disorders Vomiting	0.00% 0/21 • From the initiation of the trial till data cut-off date (15 July 2013)	14.3% 1/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Infections and infestations Pneumonia	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	14.3% 1/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Infections and infestations Septic shock	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Infections and infestations Catheter site infection	0.00% 0/21 • From the initiation of the trial till data cut-off date (15 July 2013)	14.3% 1/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Metabolism and nutrition disorders Hypokalaemia	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Renal and urinary disorders Haematuria	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Renal and urinary disorders Nephrolithiasis	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Respiratory, thoracic and mediastinal disorders Haemoptysis	4.8% 1/21 • From the initiation of the trial till data cut-off date (15 July 2013)	0.00% 0/7 • From the initiation of the trial till data cut-off date (15 July 2013)
Injury, poisoning and procedural complications Feeding tube complication	0.00% 0/21 • From the initiation of the trial till data cut-off date (15 July 2013)	14.3% 1/7 • From the initiation of the trial till data cut-off date (15 July 2013)

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee The study as a whole will be published prior to any individual investigator publications. It is required that copies of all papers, abstracts, articles, etc. that contain study data are to be forward to the Sponsor for review 30 days prior to submission for publication.
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Restriction type: OTHER