Trial Outcomes & Findings for Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors (NCT NCT02367352)

NCT ID: NCT02367352

Last Updated: 2019-06-26

Results Overview

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 9 participants
• Primary outcome timeframe: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
• Results posted on: 2019-06-26

Participant Flow

Participants took part in the study at 3 investigative sites in Japan and Republic of Korea from 19 March 2015 to 23 May 2017.

Participants with a diagnosis of Advanced Solid Tumors were enrolled in a dose escalation phase to receive a starting dose of alisertib 15 mg plus paclitaxel 60 mg/m^2. The dose expansion phase was not conducted.

Participant milestones

Measure	Cohort 1 (Dose Escalation Phase) Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).	Cohort 2 (Dose Escalation Phase) Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).	Dose Expansion Cohort Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Study STARTED	9	0	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	9	0	0

Reasons for withdrawal

Measure	Cohort 1 (Dose Escalation Phase) Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).	Cohort 2 (Dose Escalation Phase) Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).	Dose Expansion Cohort Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Study Progressive disease	7	0	0
Overall Study Participant Received Alternative Therapy	1	0	0
Overall Study Adverse Event	1	0	0

Baseline Characteristics

Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Cohort 1 (Dose Escalation Phase) n=9 Participants Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Age, Continuous	57.48 years STANDARD_DEVIATION 14.621 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	7 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants
Region of Enrollment Japan	3 participants n=5 Participants
Region of Enrollment Korea, Republic Of	6 participants n=5 Participants
Height	162.77 cm STANDARD_DEVIATION 6.907 • n=5 Participants
Weight	63.70 kg STANDARD_DEVIATION 10.165 • n=5 Participants
Body Surface Area	1.693 m^2 STANDARD_DEVIATION 0.1542 • n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)

Population: Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Measure	Dose Expansion Cohort n=9 Participants Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.	Cohort 2 (Dose Escalation Phase) Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	9 Participants	—
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	4 Participants	—

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)

Population: Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.

The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events.

Outcome measures

Measure	Dose Expansion Cohort n=9 Participants Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.	Cohort 2 (Dose Escalation Phase) Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings Neutrophil Count Decreased	5 Participants	—
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings White Blood Cell Count Decreased	4 Participants	—
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings Blood Antidiuretic Hormone Abnormal	1 Participants	—

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)

Population: Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.

The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events.

Outcome measures

Measure	Dose Expansion Cohort n=9 Participants Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.	Cohort 2 (Dose Escalation Phase) Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings	1 Participants	—

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug

Population: The dose expansion phase was cancelled by the sponsor.

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug

Population: The dose expansion phase was cancelled by the sponsor.

The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose of study drug

Population: The dose expansion phase was cancelled by the sponsor.

The number of participants with any markedly abnormal vital sign values will be collected throughout study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose

Population: The dose expansion phase was cancelled by the sponsor.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months)

Population: The dose expansion phase was cancelled by the sponsor.

ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1 (Dose Escalation Phase)

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Measure	Cohort 1 (Dose Escalation Phase) n=9 participants at risk Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Respiratory, thoracic and mediastinal disorders Pneumothorax	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Disease progression	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Infections and infestations Pneumonia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer (disease progression)	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Dizziness	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.

Other adverse events

Measure	Cohort 1 (Dose Escalation Phase) n=9 participants at risk Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m\^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Gastrointestinal disorders Diarrhoea	55.6% 5/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Stomatitis	44.4% 4/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Vomiting	44.4% 4/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Constipation	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Abdominal pain	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Dyspepsia	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Nausea	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Gastrointestinal disorders Intestinal perforation	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Skin and subcutaneous tissue disorders Alopecia	44.4% 4/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Skin and subcutaneous tissue disorders Rash	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Skin and subcutaneous tissue disorders Dermatitis acneiform	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Fatigue	55.6% 5/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Asthenia	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Chest pain	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Chills	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Influenza like illness	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Malaise	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
General disorders Pyrexia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Investigations Neutrophil count decreased	55.6% 5/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Investigations White blood cell count decreased	44.4% 4/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Investigations Blood antidiuretic hormone abnormal	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Metabolism and nutrition disorders Hyperglycaemia	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Metabolism and nutrition disorders Hyponatraemia	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Metabolism and nutrition disorders Decreased appetite	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Metabolism and nutrition disorders Hypophosphataemia	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Metabolism and nutrition disorders Hyperkalaemia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Neuropathy peripheral	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Dizziness	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Dysgeusia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Headache	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Paraesthesia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Nervous system disorders Peripheral sensory neuropathy	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Musculoskeletal and connective tissue disorders Back pain	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Musculoskeletal and connective tissue disorders Flank pain	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Musculoskeletal and connective tissue disorders Myalgia	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.2% 2/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Respiratory, thoracic and mediastinal disorders Productive cough	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Blood and lymphatic system disorders Anaemia	33.3% 3/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Infections and infestations Bronchitis	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Infections and infestations Pharyngitis	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Psychiatric disorders Delirium	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Psychiatric disorders Depression	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Eye disorders Dry eye	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Renal and urinary disorders Urinary retention	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
Vascular disorders Superior vena cava syndrome	11.1% 1/9 • First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER