Trial Outcomes & Findings for MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C (NCT NCT02391038)

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Results posted on

2017-03-29

Participant Flow

Participants took part in the study at 4 investigative sites in Korea, Japan, and Taiwan from 1 December 2014 to 7 October 2015. The study was terminated during the dose-escalation portion of phase 1 and phase 2 was not initiated.

Participants with a historical diagnosis of gastrointestinal carcinoma were enrolled in 1 of 3 treatment groups: MLN0264 1.2 milligram per kilogram (mg/kg), MLN0264 1.5 mg/kg or MLN0264 1.8 mg/kg during Phase 1.

Participant milestones

Participant milestones
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Overall Study STARTED	3	3	6
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Overall Study Progressive disease	3	3	6

Baseline Characteristics

MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: All Participants n=12 Participants Participants who either received MLN0264 1.2 mg/kg as starting dose, or 1.5 mg/kg, or 1.8 mg/kg infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle of Phase 1, for up to 1 year or until disease progression or unacceptable toxicity.
Age, Customized Between 45 to 78 years	12 participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Japan	4 participants n=5 Participants
Region of Enrollment Taiwan	1 participants n=5 Participants
Region of Enrollment Korea, Republic of	7 participants n=5 Participants
Histological classification Colon cancer	2 participants n=5 Participants
Histological classification Rectal cancer	2 participants n=5 Participants
Histological classification Gastric cancer	2 participants n=5 Participants
Histological classification Lymphovascular invasion	1 participants n=5 Participants
Histological classification Invasive ductal carcinoma of the pancreas	1 participants n=5 Participants
Histological classification Moderately differentiated ductal adenocarcinoma	1 participants n=5 Participants
Histological classification Adenocarcinoma not otherwise specified	1 participants n=5 Participants
Histological classification Tubular adenocarcinoma	1 participants n=5 Participants
Histological classification Moderately differentiated and descending colon	1 participants n=5 Participants
Participants With Prior Medical Condition	12 participants n=5 Participants
Participants With Surgical History With Surgical History	8 participants n=5 Participants
Participants With Surgical History Without Surgical History	4 participants n=5 Participants
Participants With Prior Anticancer Therapy	12 participants n=5 Participants
Participants With Prior Radiation Therapy With prior radiation therapy	2 participants n=5 Participants
Participants With Prior Radiation Therapy Without prior radiation therapy	10 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Therapy 0	8 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Therapy 1	4 participants n=5 Participants

PRIMARY outcome

Timeframe: Phase 1: Baseline through 30 days after the last dose of study drug (approximately up to 35 weeks)

Population: Safety population includes all participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)	10 participants	—	—

PRIMARY outcome

Timeframe: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Population: Safety population included all participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE)	4 participants	—	—

PRIMARY outcome

Timeframe: Phase 1: Up to Cycle 1 (3 weeks)

Population: The DLT-Evaluable population included all participants who either experienced DLT during Cycle 1 or received their scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT.

Toxicity evaluated as per NationalCancerInstituteCommonTerminologyCriteria for AEs (NCI CTCAE),version 4.03.DLT=any event related to MLN0264:Grade 4 neutropenia(absolute neutrophil count\[ANC\]less than\[\<\]500 cells/millimeter\[mm\]\^3); \>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle greater than (\>)2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)	0 participants	—	—

PRIMARY outcome

Timeframe: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Population: Safety population included all participants who received any amount of study drug.

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Number of Participants With Markedly Abnormal Laboratory Values Serum Chemistry	10 participants	—	—
Phase 1- Number of Participants With Markedly Abnormal Laboratory Values Hematology	12 participants	—	—
Phase 1- Number of Participants With Markedly Abnormal Laboratory Values Urinalysis	1 participants	—	—
Phase 1- Number of Participants With Markedly Abnormal Laboratory Values Coagulation	5 participants	—	—

PRIMARY outcome

Timeframe: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Population: Safety population included all participants who received any amount of study drug.

Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]).

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants	—	—

PRIMARY outcome

Timeframe: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Population: The DLT-Evaluable population included all participants who either experienced DLT during Cycle 1 or received their scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT.

RP2D is maximum tolerated dose(MTD) in study Phase1.MTD was highest dose of MLN0264 given at which \<=1 of 6 participants experienced DLTduring Cycle1 of Phase1.DLT=any event related to MLN0264:Grade 4 neutropenia ANC less than\<500 cells mm\^3;\>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle\>2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=12 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1- Recommended Phase 2 Dose (RP2D)	NA mg/kg None of the participants experienced DLT. Consequently, an evaluation of these participants did not establish RP2D.	—	—

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The Pharmacokinetic (PK) evaluable population included all participants who received greater than or equal to (\>=1) dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264	25.62 microgram per milliliter (mcg/mL) Standard Deviation 0.907	33.84 microgram per milliliter (mcg/mL) Standard Deviation 6.275	35.77 microgram per milliliter (mcg/mL) Standard Deviation 7.342

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264	20.99 mcg/mL Standard Deviation 0.755	29.46 mcg/mL Standard Deviation 9.180	31.11 mcg/mL Standard Deviation 6.874

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264	0.03 day Interval 0.02 to 0.03	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=4 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264	42.97 day*mcg/mL Standard Deviation 4.667	63.58 day*mcg/mL Standard Deviation 6.444	60.09 day*mcg/mL Standard Deviation 7.330

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264	31.81 day*mcg/mL Standard Deviation 11.314	74.40 day*mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	61.52 day*mcg/mL Standard Deviation 18.880

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=4 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264	41.37 day*mcg/mL Standard Deviation 4.667	59.63 day*mcg/mL Standard Deviation 6.902	57.88 day*mcg/mL Standard Deviation 7.032

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm as none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264	—	71.60 day*mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	58.03 day*mcg/mL Standard Deviation 19.233

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=4 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264	0.201 mcg/mL Standard Deviation 0.0113	0.309 mcg/mL Standard Deviation 0.0490	0.261 mcg/mL Standard Deviation 0.0831

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm as none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264	—	0.365 mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	0.369 mcg/mL Standard Deviation 0.0283

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)	24.53 mcg/mL Standard Deviation 2.179	32.12 mcg/mL Standard Deviation 9.180	36.31 mcg/mL Standard Deviation 7.709

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb	24.28 mcg/mL Standard Deviation 3.592	33.33 mcg/mL Standard Deviation 9.454	36.54 mcg/mL Standard Deviation 6.471

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb	0.03 day Interval 0.02 to 0.03	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03	0.03 day Interval 0.03 to 0.03

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=2 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=3 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb	68.82 day*mcg/mL Standard Deviation 22.910	154.95 day*mcg/mL Standard Deviation 5.657	149.65 day*mcg/mL Standard Deviation 31.321

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=1 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb	—	192.00 day*mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	204.00 day*mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb	69.82 day*mcg/mL Standard Deviation 20.647	116.59 day*mcg/mL Standard Deviation 20.775	112.46 day*mcg/mL Standard Deviation 30.653

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb	—	164.00 day*mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	147.21 day*mcg/mL Standard Deviation 32.527

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb	0.835 mcg/mL Standard Deviation 0.4912	1.479 mcg/mL Standard Deviation 0.0794	1.140 mcg/mL Standard Deviation 0.9592

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb	—	2.300 mcg/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	2.560 mcg/mL Standard Deviation 0.0424

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)	2.002 nanogram per milliliter (ng/mL) Standard Deviation 2.9479	2.335 nanogram per milliliter (ng/mL) Standard Deviation 0.3889	6.614 nanogram per milliliter (ng/mL) Standard Deviation 4.6853

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE	2.777 ng/mL Standard Deviation 5.0507	2.611 ng/mL Standard Deviation 1.1907	6.976 ng/mL Standard Deviation 5.6196

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=6 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE	2.04 day Interval 0.42 to 3.0	2.88 day Interval 2.84 to 3.0	2.45 day Interval 1.9 to 3.0

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE	2.03 day Interval 1.9 to 3.0	2.00 day Interval 2.0 to 2.92	2.89 day Interval 1.96 to 3.0

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=2 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE	8.510 day*ng/mL Standard Deviation 0.0424	17.170 day*ng/mL Standard Deviation 5.0302	53.172 day*ng/mL Standard Deviation 53.8275

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE	—	16.600 day*ng/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	37.212 day*ng/mL Standard Deviation 12.5158

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE	15.846 day*ng/mL Standard Deviation 27.9611	16.840 day*ng/mL Standard Deviation 4.7596	52.327 day*ng/mL Standard Deviation 51.8349

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE	—	16.400 day*ng/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	36.603 day*ng/mL Standard Deviation 12.1622

PRIMARY outcome

Timeframe: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg n=3 Participants MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=3 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=5 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE	0.049 ng/mL Standard Deviation 0.0665	0.037 ng/mL Standard Deviation 0.0025	0.157 ng/mL Standard Deviation 0.3717

PRIMARY outcome

Timeframe: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Outcome measures

Outcome measures
Measure	Phase 1: MLN0264 1.2 mg/kg MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.5 mg/kg n=1 Participants MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity	Phase 1: MLN0264 1.8 mg/kg n=2 Participants MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE	—	0.057 ng/mL Standard Deviation NA Standard deviation could not be calculated since only 1 participant was available for analysis.	0.117 ng/mL Standard Deviation 0.0824

SECONDARY outcome

Timeframe: Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)

Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.

Outcome measures

Outcome data not reported

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1: All Participants n=12 participants at risk Participants who either received MLN0264 1.2 mg/kg as starting dose, or 1.5 mg/kg, or 1.8 mg/kg infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle of Phase 1, for up to 1 year or until disease progression or unacceptable toxicity.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage and ascites	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Respiratory, thoracic and mediastinal disorders Asthenia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Abdominal distension	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Endocrine disorders Adrenal insufficiency	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.

Other adverse events

Other adverse events
Measure	Phase 1: All Participants n=12 participants at risk Participants who either received MLN0264 1.2 mg/kg as starting dose, or 1.5 mg/kg, or 1.8 mg/kg infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle of Phase 1, for up to 1 year or until disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Blood and lymphatic system disorders Leukopenia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Blood and lymphatic system disorders Neutropenia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Eye disorders Eye discharge	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Abdominal pain	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Ascites	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Constipation	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Diarrhoea	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Haematochezia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Melaena	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Nausea	33.3% 4/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Gastrointestinal disorders Vomiting	25.0% 3/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
General disorders Asthenia	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
General disorders Fatigue	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
General disorders Non-cardiac chest pain	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
General disorders Pyrexia	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Infections and infestations Herpes zoster	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Infections and infestations Urinary tract infection	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Injury, poisoning and procedural complications Stoma site haemorrhage	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Investigations Aspartate aminotransferase increased	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Investigations Haemoglobin decreased	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Investigations Neutrophil count decreased	33.3% 4/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Investigations Weight decreased	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Investigations White blood cell count decreased	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Metabolism and nutrition disorders Decreased appetite	33.3% 4/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Metabolism and nutrition disorders Hyperkalaemia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Metabolism and nutrition disorders Hypoalbuminaemia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Metabolism and nutrition disorders Hypokalaemia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Metabolism and nutrition disorders Hypomagnesaemia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 2/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Nervous system disorders Dizziness	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Nervous system disorders Headache	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Nervous system disorders Peripheral sensory neuropathy	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Psychiatric disorders Insomnia	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Skin and subcutaneous tissue disorders Dermatitis	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.
Vascular disorders Hypertension	8.3% 1/12 • First dose of study drug through 30 days after the last dose of any study drug (approximately 35 weeks) 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER