Trial Outcomes & Findings for A Multicentre, Open Label, Phase 1 Trial in Japan of the Mitogen Activated Protein Extracellular Signal Regulated Kinase (MEK) Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy (NCT NCT01668017)

Last Updated: 2017-08-23

Results Overview

DLT defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0): any of following toxicities possibly/probably related to study drug: Any non-hematological toxicity of Grade 3 or higher (excluding Grade 3 asymptomatic rise in liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], gamma-glutamyl transferase \[GGT\] reversible in 7 days for subjects with solid tumor and without liver involvement, or Grade 4 for subjects with HCC or with liver involvement; Grade 3 or 4 asymptomatic rise in creatinine phosphokinase (CPK) reversible in 7 days, deniable for myocardial infarction and rhabdomyolysis; Grade 3 vomiting/diarrhea encountered without optimal therapy). Any Grade 4 neutropenia \>5 days duration, any Grade 3 or above febrile neutropenia. Grade 4 thrombocytopenia \>1 day or Grade 3 with bleeding. Any treatment delay \>2 weeks due to drug-related adverse effects.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

26 participants

Primary outcome timeframe

During Treatment Cycle 1 (Day 1 to 21)

Results posted on

2017-08-23

Participant Flow

First/last subject (informed consent): September 2012/April 2015. Last subject completed: April 2015.

This study was to be conducted in 2 parts; Part 1 was the dose escalation phase and Part 2 was the expansion phase. However, due to early termination of the study, the sponsor decided not to conduct the expansion phase (Part 2).

Participant milestones

Participant milestones
Measure	Part 1: Pimasertib 30 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 30 milligram (mg) twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC) Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
Overall Study STARTED	4	9	6	5	2
Overall Study COMPLETED	4	9	6	5	2
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Multicentre, Open Label, Phase 1 Trial in Japan of the Mitogen Activated Protein Extracellular Signal Regulated Kinase (MEK) Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21- day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in HCC n=2 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Total n=26 Participants Total of all reporting groups
Age, Continuous	62.3 years STANDARD_DEVIATION 12.20 • n=5 Participants	61.4 years STANDARD_DEVIATION 10.63 • n=7 Participants	61.5 years STANDARD_DEVIATION 9.29 • n=5 Participants	58.8 years STANDARD_DEVIATION 13.63 • n=4 Participants	56.5 years STANDARD_DEVIATION 20.51 • n=21 Participants	60.7 years STANDARD_DEVIATION 11.0 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	13 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	13 Participants n=10 Participants

PRIMARY outcome

Timeframe: During Treatment Cycle 1 (Day 1 to 21)

Population: DLT analysis set included all subjects who experienced any DLT during Cycle 1 and who received above 85% of all planned doses of pimasertib during Cycle 1.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=3 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC n=1 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Number of Subjects Who Experienced at Least One Dose Limiting Toxicity (DLT)	0 subjects	0 subjects	2 subjects	1 subjects	1 subjects

SECONDARY outcome

Timeframe: Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks

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

An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC n=2 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs Serious TEAEs	2 subjects	2 subjects	2 subjects	2 subjects	0 subjects
Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs TEAEs	4 subjects	9 subjects	6 subjects	5 subjects	2 subjects

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: Pharmacokinetic (PK) analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 1	162.4 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 113.1	222.1 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 45.2	288.3 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 52.1	167.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 26.3	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.

The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	225 ng/mL	—	—	—	—
Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	281 ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Data were not reported for "Part 1: Pimasertib 45 mg in HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=5 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 15	199.5 ng/mL Geometric Coefficient of Variation 58.9	231.6 ng/mL Geometric Coefficient of Variation 66.1	336.3 ng/mL Geometric Coefficient of Variation 30.8	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	320 ng/mL	—	—	—	—
Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	419 ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 1	2.450 hours Interval 0.48 to 4.0	1.480 hours Interval 0.48 to 7.98	1.710 hours Interval 0.97 to 2.43	1.000 hours Interval 0.95 to 2.57	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	1.47 hours	—	—	—	—
Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	1.92 hours	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=5 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 15	1.805 hours Interval 1.0 to 2.48	1.910 hours Interval 1.0 to 2.48	2.550 hours Interval 1.5 to 5.88	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	0.98 hours	—	—	—	—
Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	0.95 hours	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration Over Time (AUCt) at Cycle 1 Day 1	703.0 h*ng/mL Geometric Coefficient of Variation 73.8	862.4 h*ng/mL Geometric Coefficient of Variation 42.8	1626.9 h*ng/mL Geometric Coefficient of Variation 43.6	911.4 h*ng/mL Geometric Coefficient of Variation 27.3	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	1754 h*ng/mL	—	—	—	—
Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	1430 h*ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours).

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=8 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 1	618.3 h*ng/mL Geometric Coefficient of Variation 86.1	857.4 h*ng/mL Geometric Coefficient of Variation 46.0	1629.3 h*ng/mL Geometric Coefficient of Variation 43.7	911.7 h*ng/mL Geometric Coefficient of Variation 27.2	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	1761 h*ng/mL	—	—	—	—
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	1431 h*ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 15	1189.3 h*ng/mL Geometric Coefficient of Variation 73.6	1125.0 h*ng/mL Geometric Coefficient of Variation 62.1	2140.7 h*ng/mL Geometric Coefficient of Variation 37.6	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	2250 h*ng/mL	—	—	—	—
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	1687 h*ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

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: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=8 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=5 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 1	3.480 hours Interval 3.43 to 4.78	3.545 hours Interval 2.77 to 5.24	3.935 hours Interval 2.71 to 5.61	4.560 hours Interval 3.27 to 11.5	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

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. The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	5.68 hours	—	—	—	—
Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	5.46 hours	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

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. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 15	4.235 hours Interval 0.775 to 5.21	4.000 hours Interval 3.13 to 5.71	5.530 hours Interval 2.92 to 8.24	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	15.4 hours	—	—	—	—
Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	5.41 hours	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=7 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=5 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=3 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Clearance (CL/f) of Pimasertib on Cycle 1 Day 1	41.67 liter/hour (L/h) Geometric Coefficient of Variation 80.5	48.17 liter/hour (L/h) Geometric Coefficient of Variation 52.8	32.62 liter/hour (L/h) Geometric Coefficient of Variation 54.6	32.19 liter/hour (L/h) Geometric Coefficient of Variation 27.3	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	18.5 L/h	—	—	—	—
Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	23.7 L/h	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Clearance at Steady-state (CLss/f) of Pimasertib on Cycle 1 Day 15	25.24 L/h Geometric Coefficient of Variation 73.6	40.00 L/h Geometric Coefficient of Variation 62.1	28.02 L/h Geometric Coefficient of Variation 37.6	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The summarized data was not available for this arm therefore individual data was presented.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	13.3 L/h	—	—	—	—
Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	17.8 L/h	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

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: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=7 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=5 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=3 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 1	231.2 liters Geometric Coefficient of Variation 71.6	238.1 liters Geometric Coefficient of Variation 46.7	169.8 liters Geometric Coefficient of Variation 29.7	177.2 liters Geometric Coefficient of Variation 15.9	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 1	152 liters	—	—	—	—
Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1 Subject 2	187 liters	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 15	105.0 liters Geometric Coefficient of Variation 161.1	233.9 liters Geometric Coefficient of Variation 46.4	209.1 liters Geometric Coefficient of Variation 10.6	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 1	297 liters	—	—	—	—
Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15 Subject 2	139 liters	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Accumulation Ratio for AUC Racc(AUC) of Pimasertib	1.782 ratio Geometric Coefficient of Variation 4.2	1.382 ratio Geometric Coefficient of Variation 30.2	1.311 ratio Geometric Coefficient of Variation 51.5	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15

Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm Subject 1	2.43 ratio	—	—	—	—
Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm Subject 2	1.83 ratio	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15

Population: PK analysis set. Here "Overall Number of Participants Analyzed" signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.

Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax). Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=6 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=5 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Accumulation Ratio for Cmax Racc(Cmax) of Pimasertib	1.227 ratio Geometric Coefficient of Variation 38.3	0.8281 ratio Geometric Coefficient of Variation 65.5	1.215 ratio Geometric Coefficient of Variation 61.3	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15

Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax).

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=2 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm Subject 1	1.50 ratio	—	—	—	—
Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm Subject 2	2.31 ratio	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)

Population: Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.

Percentage of subjects with best overall response in each category (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=7 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=4 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC n=2 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Percentage of Subjects With Best Overall Response CR	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects
Percentage of Subjects With Best Overall Response PR	0 percentage of subjects	42.9 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects
Percentage of Subjects With Best Overall Response SD	0 percentage of subjects	14.3 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects
Percentage of Subjects With Best Overall Response PD	66.7 percentage of subjects	42.9 percentage of subjects	75.0 percentage of subjects	75.0 percentage of subjects	50.0 percentage of subjects
Percentage of Subjects With Best Overall Response Not evaluable	33.3 percentage of subjects	0 percentage of subjects	25.0 percentage of subjects	25.0 percentage of subjects	50.0 percentage of subjects

SECONDARY outcome

Timeframe: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)

Population: Efficacy analysis set' included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.

Percentage of subjects with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=7 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=4 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC n=2 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Percentage of Subjects With Objective Response	0 percentage of subjects	42.9 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects

SECONDARY outcome

Timeframe: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)

Population: Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.

Percentage of subjects with disease control (CR plus PR plus greater than 12 weeks SD) according to RECIST Version 1.1 was reported CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=3 Participants Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=7 Participants Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=4 Participants Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 30 mg in HCC n=4 Participants Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.	Part 1: Pimasertib 45 mg in HCC n=2 Participants Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Percentage of Subjects With Disease Control	0 percentage of subjects	57.1 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects

Adverse Events

Part 1: Pimasertib 30 mg in Solid Tumor

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 1: Pimasertib 45 mg in Solid Tumor

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Part 1: Pimasertib 60 mg in Solid Tumor

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1: Pimasertib 30 mg in HCC

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 1: Pimasertib 45 mg in HCC

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 participants at risk Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 participants at risk Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 participants at risk Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 30 mg in HCC n=5 participants at risk Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in HCC n=2 participants at risk Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
General disorders Disease progression	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders General physical health deterioration	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Pyrexia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Hepatobiliary disorders Liver disorder	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Infection	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks

Other adverse events

Other adverse events
Measure	Part 1: Pimasertib 30 mg in Solid Tumor n=4 participants at risk Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in Solid Tumor n=9 participants at risk Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 60 mg in Solid Tumor n=6 participants at risk Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 30 mg in HCC n=5 participants at risk Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.	Part 1: Pimasertib 45 mg in HCC n=2 participants at risk Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
Investigations Weight decreased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Decreased appetite	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	44.4% 4/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 3/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Hypoalbuminaemia	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Blood and lymphatic system disorders Leukopenia	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Cardiac disorders Pericardia effusion	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Retinal detachment	75.0% 3/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 6/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	83.3% 5/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	60.0% 3/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Vision blurred	75.0% 3/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 6/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	83.3% 5/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	60.0% 3/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Retinal haemorrhage	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Visual impairment	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Macular oedema	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Ocular hypertension	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Retinal tear	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Macular detachment	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Metamorphopsia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Visual acuity reduced	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Eye disorders Vitreous floaters	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	55.6% 5/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 3/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	60.0% 3/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Nausea	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 3/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Stomatitis	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 4/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Vomiting	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 3/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	100.0% 2/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Constipation	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Ascites	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Cheilitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Dyspepsia	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Gastritis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Gastrointestinal disorders Oesophagitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Oedema peripheral	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	55.6% 5/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 4/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Pyrexia	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 3/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Localised oedema	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Fatigue	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Malaise	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Influenza like illness	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Face oedema	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
General disorders Feeling hot	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Hepatobiliary disorders Cholangitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Immune system disorders Contrast media allergy	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Conjunctivitis	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Cystitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Infection	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Laryngitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Nasopharyngitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Paronychia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Infections and infestations Pharyngitis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Injury, poisoning and procedural complications Frostbite	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Blood creatine phosphokinase increased	100.0% 4/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 6/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	83.3% 5/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Aspartate aminotransferase increased	75.0% 3/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	55.6% 5/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Alanine aminotransferase increased	50.0% 2/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Blood lactate dehydrogenase increased	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Blood alkaline phosphatase increased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	22.2% 2/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Blood creatine phosphokinase MB increased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Blood creatinine increased	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Electrocardiogram QT prolonged	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Fibrin D dimer increased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Haemoglobin decreased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Platelet count decreased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Weight increased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations White blood cell count decreased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Investigations Gamma-glutamyltransferase increased	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	40.0% 2/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Hypomagnesaemia	50.0% 2/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Back pain	50.0% 2/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Muscular weakness	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Nervous system disorders Lethargy	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Nervous system disorders Presyncope	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Nervous system disorders Syncope	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Nervous system disorders Headache	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Psychiatric disorders Delirium	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Psychiatric disorders Confusional state	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Reproductive system and breast disorders Menstruation irregular	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Dermatitis acneiform	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	66.7% 6/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 3/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	80.0% 4/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Dry skin	50.0% 2/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 3/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Rash	50.0% 2/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	33.3% 2/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	20.0% 1/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	50.0% 1/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Urticaria	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	11.1% 1/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	16.7% 1/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
Skin and subcutaneous tissue disorders Skin ulcer	25.0% 1/4 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/9 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/6 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/5 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks	0.00% 0/2 • Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks

Additional Information

Merck KGaA Communication Center

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Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place