Trial Outcomes & Findings for A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Trebananib (AMG 386 ) in Adult Japanese Participants With Advanced Solid Tumors (NCT NCT02525536)

Last Updated: 2015-09-22

Results Overview

DLT is defined as any treatment-related, grade 4 or higher hematologic or grade 3 or higher non-hematologic toxicity (according to the Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0; hematologic toxicity means any toxicities which are categorized in blood/bone marrow category of CTCAE), except for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and infusion reaction, occurred during the first 28 days after the initial administration (before examination on Study Day 29). DLT also includes AST or ALT: \>10\*upper limit of normal (ULN) international units per liter (IU/L).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

Day 1 up to Day 28

Results posted on

2015-09-22

Participant Flow

Participants took part in the study at 1 investigative site in Japan from 26 June 2009 to 28 May 2014.

Participants with a historical diagnosis of advanced solid tumor were enrolled in 1 of 3 treatment groups: trebananib 3 milligram/kilogram (mg/kg); trebananib 10 mg/kg; trebananib 30 mg/kg.

Participant milestones

Participant milestones
Measure	Trebananib 3 mg/kg Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Overall Study STARTED	6	6	6
Overall Study COMPLETED	6	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Trebananib (AMG 386 ) in Adult Japanese Participants With Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Total n=18 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 10.41 • n=5 Participants	55.3 years STANDARD_DEVIATION 7.71 • n=7 Participants	60.7 years STANDARD_DEVIATION 6.71 • n=5 Participants	57.9 years STANDARD_DEVIATION 8.22 • n=4 Participants
Age, Customized Less than (<) 65 years	4 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	12 participants n=4 Participants
Age, Customized Greater than or equal to (>=) 65 years	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Height	162.28 centimeter STANDARD_DEVIATION 6.233 • n=5 Participants	161.08 centimeter STANDARD_DEVIATION 12.788 • n=7 Participants	160.48 centimeter STANDARD_DEVIATION 3.136 • n=5 Participants	161.28 centimeter STANDARD_DEVIATION 7.938 • n=4 Participants
Weight	52.80 kilogram STANDARD_DEVIATION 10.208 • n=5 Participants	64.03 kilogram STANDARD_DEVIATION 10.623 • n=7 Participants	50.40 kilogram STANDARD_DEVIATION 3.683 • n=5 Participants	55.74 kilogram STANDARD_DEVIATION 10.257 • n=4 Participants
Medical and surgical history With medical and surgical history	6 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	15 participants n=4 Participants
Medical and surgical history Without medical and surgical history	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Primary Tumor Type Neoplasm, stomach	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Primary Tumor Type Neoplasm, rectal	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Primary Tumor Type Neoplasm, pancreatic	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Primary Tumor Type Neoplasm, colon	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Primary Tumor Type Neoplasm, bladder	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Primary Tumor Type Neoplasm, breast	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Primary Tumor Type Neoplasm, uterine	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Prior Radiotherapy With prior radiotherapy	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Prior Radiotherapy Without prior radiotherapy	6 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants
Prior Other Cancer Medication With prior other cancer medication	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Prior Other Cancer Medication Without prior other cancer medication	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG performance status 0	6 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	17 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG performance status 1	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Method of Tumor Assessment Computed Tomography (CT)	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Method of Tumor Assessment Magnetic Resonance Imaging (MRI)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Number of Target Lesions 1 Target Lesion	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Number of Target Lesions 2 Target Lesion	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants
Number of Target Lesions 3 Target Lesion	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Number of Target Lesions 4 Target Lesion	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Number of Target Lesions >=5 Target Lesion	2 participants n=5 Participants	5 participants n=7 Participants	1 participants n=5 Participants	8 participants n=4 Participants
Sum of the Longest Diameter of Target Lesions	112.3 millimeters STANDARD_DEVIATION 98.70 • n=5 Participants	179.3 millimeters STANDARD_DEVIATION 99.23 • n=7 Participants	96.8 millimeters STANDARD_DEVIATION 63.07 • n=5 Participants	129.5 millimeters STANDARD_DEVIATION 91.04 • n=4 Participants
Presence of Non-Target Lesions With Non-Target Lesions	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Presence of Non-Target Lesions Without Non-Target Lesions	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Region of Enrollment	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 28

Population: DLT analysis set: all participants who experience at least 1 DLT in the first 28 days of treatment, or who received all planned AMG 386 dose and are followed until the day before the treatment on Study Day 29.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants With Dose Limiting Toxicity (DLT)	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

Population: Safety analysis set: all participants who received at least 1 dose of AMG 386.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. Treatment emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants Reporting One or More Treatment-emergent Adverse Events (AEs) and Serious Adverse Event (SAEs) SAEs	2 participants	0 participants	1 participants
Number of Participants Reporting One or More Treatment-emergent Adverse Events (AEs) and Serious Adverse Event (SAEs) AEs	6 participants	6 participants	6 participants

PRIMARY outcome

Timeframe: Week 1: predose, 1, 6 hours after end of infusion, Week 4: predose, 1 hour after end of infusion, Week 8, 16: predose, thereafter predose of every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

Population: Safety analysis set: all participants who received at least 1 dose of AMG 386.

Change relative to baseline in electrocardiogram measured throughout study. Significant change in ECG observed at any time point was summarized and reported.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants With Significant Change From Baseline in Electrocardiogram (ECG)	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after infusion end, Week 2, 3, 4: predose and 1 hour after infusion end, thereafter predose of every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)

Population: Safety analysis set: all participants who received at least 1 dose of AMG 386.

Vital signs included body temperature, diastolic and systolic blood pressure, and pulse (beats per minutes). clinically significant change in vital signs observed at any time point was summarized and reported.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Week 1: predose, 24, 48 and 96 hours after infusion end, Week 2 and 3: predose, Week 4: predose and 1 hour after infusion end, thereafter every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)

Population: Safety analysis set: all participants who received at least 1 dose of AMG 386.

The number of participants with any abnormal standard safety laboratory values collected throughout study. Parameters assessed were hematology, chemistry, coagulation and urinalysis. Abnormal laboratory values observed at any time point was summarized and reported.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants With Abnormal Laboratory Values Chemistry	6 participants	6 participants	6 participants
Number of Participants With Abnormal Laboratory Values Hematology	5 participants	4 participants	6 participants
Number of Participants With Abnormal Laboratory Values Coagulation	3 participants	0 participants	0 participants
Number of Participants With Abnormal Laboratory Values Urinalysis	2 participants	2 participants	3 participants

PRIMARY outcome

Timeframe: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 1 assessment available.

Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Cmax: Maximum Observed Serum Concentration for AMG 386 After Week 1 Dose	52.33 microgram per milliliter (mcg/mL) Standard Deviation 11.27	239.0 microgram per milliliter (mcg/mL) Standard Deviation 47.11	551.2 microgram per milliliter (mcg/mL) Standard Deviation 86.76

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Cmax is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Cmax: Maximum Observed Serum Concentration for AMG 386 After Week 4 Dose	59.02 mcg/mL Standard Deviation 10.09	277.0 mcg/mL Standard Deviation 48.79	688.7 mcg/mL Standard Deviation 104.5

PRIMARY outcome

Timeframe: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 1 assessment available.

Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for AMG 386 After Week 1 Dose	1.067 hour (hr) Full Range 582.1 • Interval 1.033 to 1.083	1.033 hour (hr) Full Range 924.5 • Interval 1.017 to 1.05	1.167 hour (hr) Full Range 4489 • Interval 1.017 to 2.0

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for AMG 386 After Week 4 Dose	1.067 hr Full Range 35.05 • Interval 1.017 to 2.033	1.017 hr Full Range 14.84 • Interval 1.017 to 2.017	1.508 hr Full Range 25.57 • Interval 1.033 to 2.017

PRIMARY outcome

Timeframe: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 1 assessment available.

AUC (0-tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen).

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
AUC (0-tau): Area Under the Serum Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for AMG 386 After Week 1 Dose	1760 microgramhour/milliliter (mcghr/mL) Standard Deviation 582.1	4629 microgramhour/milliliter (mcghr/mL) Standard Deviation 924.5	18040 microgramhour/milliliter (mcghr/mL) Standard Deviation 4489

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

AUC (0-tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen).

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
AUC (0-tau): Area Under the Serum Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for AMG 386 After Week 4 Dose	2171 mcg*hr/mL Standard Deviation 715.4	5880 mcg*hr/mL Standard Deviation 559.6	21170 mcg*hr/mL Standard Deviation 2912

PRIMARY outcome

Timeframe: Week 2: predose

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 1 assessment available.

Cmin was the observed serum concentration at 168 hours postdose.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Cmin: Minimum Observed Serum Trough Concentration for AMG 386 After Week 1 Dose	2.702 mcg/mL Standard Deviation 1.226	3.857 mcg/mL Standard Deviation 1.018	20.20 mcg/mL Standard Deviation 5.060

PRIMARY outcome

Timeframe: Week 4: 168 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Cmin was the observed serum concentration at 168 hours postdose.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Cmin: Minimum Observed Serum Trough Concentration for AMG 386 After Week 4 Dose	5.323 mcg/mL Standard Deviation 2.536	7.266 mcg/mL Standard Deviation 1.521	45.07 mcg/mL Standard Deviation 16.24

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state, estimated as: Vss = MRTinf \*CLss, where MRTinf is mean residence time of drug extrapolated to infinity and CLss is the systemic clearance at the steady state. Vss was normalized to participant's body weight.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Vss: Volume of Distribution at Steady State for AMG 386	158.2 milliliter per kilogram (mL/kg) Standard Deviation 49.02	121.0 milliliter per kilogram (mL/kg) Standard Deviation 22.18	136.6 milliliter per kilogram (mL/kg) Standard Deviation 30.26

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Terminal Phase Elimination Half-life (T1/2) for AMG 386	95.86 hr Standard Deviation 35.05	95.41 hr Standard Deviation 14.84	93.89 hr Standard Deviation 25.57

PRIMARY outcome

Timeframe: Week 4: predose, 1, 2, 6, 24, 48, 96 and 168 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

CL is a quantitative measure of the rate at which a drug substance is removed from the body. Systemic clearance at steady state (CLss) was calculated as the ratio of dose administered to AUC (0 - tau), where AUC (0 - tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen). CLss was normalized to participant's body weight.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Systemic Clearance at Steady State (CLss) for AMG 386	1.495 milliliter/hour/kilogram(mL/hr/kg) Standard Deviation 0.4231	1.713 milliliter/hour/kilogram(mL/hr/kg) Standard Deviation 0.1653	1.439 milliliter/hour/kilogram(mL/hr/kg) Standard Deviation 0.1912

PRIMARY outcome

Timeframe: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose, Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion

Population: Pharmacokinetic analysis set: all participants who had at least 1 evaluable serum concentrations, received at least 1 dose of AMG 386, and had Week 4 assessment available.

Accumulation ratio (AR) was calculated by dividing the individual AUC (0-tau) value at Week 4 by the corresponding individual AUC (0-tau) value at Week 1.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=5 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Accumulation Ratio (AR) for AMG 386	1.235 ratio Standard Deviation 0.05143	1.193 ratio Standard Deviation 0.06862	1.211 ratio Standard Deviation 0.2139

SECONDARY outcome

Timeframe: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

Population: Response evaluable analysis set: a subset of participants in the full analysis set (FAS) with at least 1 measurable lesion at baseline using the RECIST 1.0. FAS consisted of all participants who had evaluable data and received at least 1 dose of AMG 386.

Best overall response for a participant is the best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Complete Response (CR): disappearance of all target lesions, non-target lesions and normalization of tumor marker level. Partial Response (PR): at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the baseline smallest sum of longest diameter; persistence of 1 or more non-target lesion(s) or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participants With Best Overall Response CR	0 participants	0 participants	0 participants
Number of Participants With Best Overall Response PR	1 participants	0 participants	1 participants
Number of Participants With Best Overall Response SD	0 participants	1 participants	1 participants
Number of Participants With Best Overall Response PD	5 participants	5 participants	4 participants

SECONDARY outcome

Timeframe: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

Population: Response evaluable analysis set: a subset of participants in the FAS with at least 1 measurable lesion at baseline using the RECIST 1.0. FAS consisted of all participants who had evaluable data and received at least 1 dose of AMG 386.

Objective response rate defined as the rate of participants with CR or PR based on RECIST 1.0 criteria. CR: disappearance of all target lesions, non-target lesions and normalization of tumor marker level. PR: at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Percentage of Participants With Objective Response	17 Percentage of participants Interval 0.4 to 64.1	0 Percentage of participants Interval 0.0 to 39.3	17 Percentage of participants Interval 0.4 to 64.1

SECONDARY outcome

Timeframe: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

TTP is defined as the time from the date of first administration of study treatment to the date of first documentation of PD or death caused by progression. For participants who did not have a documented PD or died owing to causes other than progression, TTP was censored at the time of last response assessment. PD is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Time to Progression (TTP)	48.0 Days Interval 26.0 to 1221.0	46.0 Days Interval 15.0 to 150.0	45.5 Days Interval 45.0 to 718.0

SECONDARY outcome

Timeframe: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249

Population: Response evaluable analysis set: a subset of participants in the FAS with at least 1 measurable lesion at baseline using the RECIST 1.0 and valid post-baseline tumor lesion assessment available. FAS consisted of all participants who had evaluable data and received at least 1 dose of AMG 386.

The percent change from baseline to post-baseline is the largest percent reduction from baseline among all post-dose measures of the sum of the longest diameter of the tumor burden.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=5 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Percent Change From Baseline to Post-baseline in the Sum of the Longest Diameters of Tumor	-1.53 percent change Standard Deviation 48.655	16.36 percent change Standard Deviation 18.455	5.53 percent change Standard Deviation 46.907

SECONDARY outcome

Timeframe: Week 1: predose,1,2,6,24,48 and 98 hours after infusion end, Week 3: predose, Week 4: predose, 1,2,6,24,48,96,168 and 264 hours after infusion end, thereafter predose every 4 weeks starting from Week 8 up to 8 weeks after last dose (last dose=Week 249)

Population: Safety analysis set: all participants who received at least 1 dose of AMG 386.

The immunogenicity of AMG 386 was evaluated with an immunoassay that detects anti-AMG 386 binding antibodies. Antibody formation reported at any of the time points was summarized.

Outcome measures

Outcome measures
Measure	Trebananib 3 mg/kg n=6 Participants Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 Participants Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 Participants Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Number of Participant With Anti-AMG 386 Antibody	2 participants	1 participants	0 participants

Adverse Events

Trebananib 3 mg/kg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Trebananib 10 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Trebananib 30 mg/kg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trebananib 3 mg/kg n=6 participants at risk Trebananib (AMG 386) 3 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 10 mg/kg n=6 participants at risk Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).	Trebananib 30 mg/kg n=6 participants at risk Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
Gastrointestinal disorders Ascites	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.
Hepatobiliary disorders Cholecystitis	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small intestine carcinoma	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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 Pleural effusion	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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 Subclavian vein thrombosis	16.7% 1/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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.	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of the study drug and no more than 28 days after the last dose of study drug. 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

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER