Trial Outcomes & Findings for AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib (NCT NCT00853372)

Last Updated: 2020-07-01

Results Overview

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: an AE that: is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an other significant medical hazard. Treatment-emergent AEs (TEAEs) are those that occurred after the first administration of study drug through 30 days after the last study drug administration. Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

85 participants

Primary outcome timeframe

From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.

Results posted on

2020-07-01

Participant Flow

This study was conducted at 18 sites in the United States, Australia, Belgium, France, and Poland. The first participant was enrolled on 28 May 2009. The last participant was enrolled on 29 November 2010.

Participant milestones

Participant milestones
Measure	Trebananib 10 mg/kg + Sunitinib Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Overall Study STARTED	43	42
Overall Study COMPLETED	11	13
Overall Study NOT COMPLETED	32	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Trebananib 10 mg/kg + Sunitinib Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Overall Study Death	30	26
Overall Study Lost to Follow-up	1	2
Overall Study Full Consent Withdrawn	1	1

Baseline Characteristics

AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Total n=85 Participants Total of all reporting groups
Age, Customized < 65 years	30 participants n=99 Participants	27 participants n=107 Participants	57 participants n=206 Participants
Age, Customized >= 65 years	13 participants n=99 Participants	15 participants n=107 Participants	28 participants n=206 Participants
Age, Customized < 75 years	41 participants n=99 Participants	40 participants n=107 Participants	81 participants n=206 Participants
Age, Customized >= 75 years	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	10 Participants n=107 Participants	15 Participants n=206 Participants
Sex: Female, Male Male	38 Participants n=99 Participants	32 Participants n=107 Participants	70 Participants n=206 Participants
Race/Ethnicity, Customized White or Caucasian	41 participants n=99 Participants	42 participants n=107 Participants	83 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Asian	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Japanese	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Aborigine	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Other, Not Specified	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs, All	43 participants	42 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs, Grade ≥ 3	32 participants	34 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs, Grade ≥ 4	4 participants	7 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs, Fatal AEs	1 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs, SAEs	17 participants	26 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs Leading to (→) DC of Trebananib	7 participants	14 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of Trebananib, Serious	5 participants	12 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of Trebananib, Non-Serious	2 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of Sunitinib	9 participants	16 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of Sunitinib, Serious	5 participants	12 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of Sunitinib, Non-Serious	4 participants	5 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of All Treatment	6 participants	14 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of All Treatment, Serious	5 participants	12 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TEAEs → DC of All Treatment, Non-Serious	1 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) Treatment-Related (TR) TEAEs, All	43 participants	42 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs, Grade ≥ 3	25 participants	31 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs, Grade ≥ 4	2 participants	5 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs, Fatal AEs	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs, SAEs	11 participants	18 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Trebananib	6 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Trebananib, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Trebananib, Non-Serious	2 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Sunitinib	8 participants	15 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Sunitinib, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of Sunitinib, Non-Serious	4 participants	5 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of All Treatment	5 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of All Treatment, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TR TEAEs → DC of All Treatment, Non-Serious	1 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) Trebananib-Related (TrR) TEAEs, All	34 participants	39 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs, Grade ≥ 3	17 participants	19 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs, Grade ≥ 4	1 participants	4 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs, Fatal AEs	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs, SAEs	10 participants	15 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Trebananib	6 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Trebananib, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Trebananib, Non-Serious	2 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Sunitinib	6 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Sunitinib, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of Sunitinib, Non-Serious	2 participants	3 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of All Treatment	5 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of All Treatment, Serious	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) TrR TEAEs → DC of All Treatment, Non-Serious	1 participants	2 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) Sunitinib-Related (SR) TEAEs, All	43 participants	42 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs, Grade ≥ 3	25 participants	31 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs, Grade ≥ 4	2 participants	5 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs, Fatal AEs	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs, SAEs	9 participants	15 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of Trebananib	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of Trebananib, Serious	3 participants	10 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of Trebananib, Non-Serious	1 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC Sunitinib	7 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of Sunitinib, Serious	3 participants	10 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of Sunitinib, Non-Serious	4 participants	4 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of All Treatment	4 participants	11 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of All Treatment, Serious	3 participants	10 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) SR TEAEs → DC of All Treatment, Non-Serious	1 participants	1 participants

PRIMARY outcome

Timeframe: Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.

Population: Safety Analysis Set: participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

A trebananib dose was considered delayed if it was administered 11 or more days from the previous trebananib infusion. A sunitinib dose was considered delayed if it was administered 3 or more days from the previous dose, except during holidays.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Number of Participants With Dose Delays Due to Adverse Events Trebananib Dose Delays	26 participants	28 participants
Number of Participants With Dose Delays Due to Adverse Events Sunitinib Dose Delays	29 participants	27 participants

PRIMARY outcome

Timeframe: first 12 weeks of study treatment

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Participants who had a sunitinib dose modification within 12 weeks from their first dose due to adverse event, laboratory toxicity, or laboratory toxicity and adverse event.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose Any Dose Modification (DM)	25 participants	24 participants
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose DM Due to Adverse Event	20 participants	18 participants
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose DM Due to Laboratory Toxicity	4 participants	4 participants
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose DM Due to Laboratory Toxicity and Adverse Event	1 participants	2 participants

PRIMARY outcome

Population: Safety Aanalysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Total Bilirubin, AN	0 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Alanine Aminotransferase, Above Normal (AN)	3 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Albumin, Below Normal (BN)	1 participants	1 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Alkaline Phosphatase, AN	0 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Amylase, AN	2 participants	5 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Aspartate Aminotransferase, AN	2 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Glucose, AN	1 participants	3 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Glucose, BN	1 participants	0 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Lipase, AN	5 participants	7 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Magnesium, BN	0 participants	1 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Phosphorus, BN	3 participants	4 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Potassium, BN	2 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Sodium, BN	1 participants	4 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Absolute Neutrophil Count, BN	3 participants	5 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Hemoglobin, BN	1 participants	3 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Lymphocytes, BN	6 participants	3 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Partial Thromboplastin Time, AN	1 participants	1 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Platelets, BN	3 participants	2 participants
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values Total Neutrophils, BN	3 participants	5 participants

SECONDARY outcome

Timeframe: 48 months after last subject enrolled (LSE)

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease.

ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) per modified Response Evaluation Criteria in Solid Tumor (RECIST) criteria (responder). A confirmed CR requires 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. All participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non responders.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=41 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Objective Response Rate (ORR)	58.1 percentage of participants Interval 47.2 to 68.5	63.4 percentage of participants Interval 52.2 to 73.6

SECONDARY outcome

Timeframe: 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with an objective response.

DOR was calculated as the time from the first confirmed objective response to first observed disease progression per modified RECIST v. 1.0 criteria or death due to any cause. DOR was calculated only for participants who had an objective response. Objective response was defined as either a confirmed CR or PR per modified RECIST criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR required 2 consecutive assessments at least 28 days apart of PR or CR. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable radiographical disease assessment date.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=25 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=26 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Kaplan-Meier Estimate: Duration of Response (DOR)	18.0 months Interval 11.8 to 24.4	18.4 months Interval 11.5 to 24.8

SECONDARY outcome

Timeframe: 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease.

DCR was defined as the percentage of participants with confirmed CR or PR or stable disease (SD), as defined by modified RECIST v1.0 criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. CR or PR was confirmed at least 28 days after the criteria for response were first met. A response assessment of PR or CR that was not subsequently confirmed at least 4 weeks later were included as SD.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=41 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Disease Control Rate (DCR)	72.1 percentage of participants Interval 61.5 to 81.0	75.6 percentage of participants Interval 64.9 to 84.3

SECONDARY outcome

Timeframe: 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

PFS was defined as the time from enrollment date to date of disease progression (ie, radiographic progression) per modified RECIST v 1.0 criteria or death. Radiological imaging to assess disease status was performed until participants developed disease progression. Events of radiographic progression per modified RECIST 1.0 that occurred after initiation of subsequent anticancer therapy were not considered PFS events. Deaths occurring after initiation of subsequent anticancer therapy were considered PFS events. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Kaplan-Meier Estimate: Progression Free Survival (PFS)	13.9 months Interval 11.0 to 16.1	16.5 months Interval 13.3 to 21.4

SECONDARY outcome

Timeframe: 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

The time from enrollment date to date of death. Participants who had not died by the analysis data cutoff date were censored at their last contact date.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=43 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=42 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Kaplan-Meier Estimate: Overall Survival (OS)	36.0 months Interval 26.0 to 52.9	38.7 months Interval 31.5 to 42.6

SECONDARY outcome

Timeframe: Baseline, 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease and non-missing baseline and post-baseline data.

Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=41 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=40 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir	-36.0 percent reduction in SLD Interval -43.4 to -28.6	-41.8 percent reduction in SLD Interval -48.4 to -35.3

SECONDARY outcome

Timeframe: Pre-infusion and up to 10 minutes post-infusion on Weeks 1, 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)

Population: Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=38 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=41 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 1	222 µg/mL Interval 63.2 to 819.0	297 µg/mL Interval 152.0 to 535.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 4	285 µg/mL Interval 82.4 to 574.0	377 µg/mL Interval 258.0 to 647.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 7	260 µg/mL Interval 75.3 to 550.0	377 µg/mL Interval 238.0 to 1830.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 10	257 µg/mL Interval 105.0 to 630.0	476 µg/mL Interval 184.0 to 770.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 13	219 µg/mL Interval 105.0 to 390.0	385 µg/mL Interval 216.0 to 785.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 22	249 µg/mL Interval 92.8 to 385.0	417 µg/mL Interval 224.0 to 758.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 34	240 µg/mL Interval 137.0 to 628.0	387 µg/mL Interval 77.7 to 571.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 46	221 µg/mL Interval 159.0 to 700.0	349 µg/mL Interval 235.0 to 908.0
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 58	229 µg/mL Interval 158.0 to 606.0	—
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 70	185 µg/mL Interval 108.0 to 362.0	—
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 82	223 µg/mL Interval 94.1 to 272.0	—
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 94	270 µg/mL Interval 173.0 to 367.0	—
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Week 106	289 µg/mL Interval 289.0 to 289.0	—
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time Safety Follow-Up	3.46 µg/mL Interval 1.26 to 6.16	8.26 µg/mL Interval 5.62 to 11.8

SECONDARY outcome

Timeframe: Pre-infusion on Weeks 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)

Population: Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=38 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=29 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 4	20.4 µg/mL Interval 6.22 to 41.9	27.3 µg/mL Interval 6.35 to 95.4
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 7	30.1 µg/mL Interval 12.2 to 75.9	42.0 µg/mL Interval 14.9 to 90.4
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 10	23.3 µg/mL Interval 9.09 to 72.3	32.2 µg/mL Interval 13.9 to 85.6
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 13	26.1 µg/mL Interval 8.54 to 73.8	43.2 µg/mL Interval 15.1 to 99.5
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 22	19.9 µg/mL Interval 8.59 to 63.1	46.2 µg/mL Interval 16.2 to 73.7
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 34	24.1 µg/mL Interval 9.88 to 66.2	35.9 µg/mL Interval 15.3 to 79.2
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 46	23.2 µg/mL Interval 6.46 to 64.4	30.5 µg/mL Interval 21.0 to 71.8
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 58	27.9 µg/mL Interval 8.61 to 43.3	—
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 70	26.2 µg/mL Interval 10.5 to 35.9	—
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 82	22.5 µg/mL Interval 17.9 to 33.0	—
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 94	25.9 µg/mL Interval 19.9 to 31.8	—
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Week 106	19.3 µg/mL Interval 19.3 to 19.3	—
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time Safety Follow-Up	3.46 µg/mL Interval 1.26 to 6.16	8.26 µg/mL Interval 5.62 to 11.8

SECONDARY outcome

Timeframe: Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)

Population: Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. Per protocol, this outcome measure evaluated a sub-group of participants at selected sites outside of Europe.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=9 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=7 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 4	58.6 ng/mL Interval 41.1 to 124.0	70.6 ng/mL Interval 50.8 to 105.0
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 7	0.763 ng/mL Interval to 4.68 below lower limit of quantification (0.25 ng/mL)	1.65 ng/mL Interval to 3.78 below lower limit of quantification (0.25 ng/mL)
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 10	66.1 ng/mL Interval 46.7 to 136.0	64.7 ng/mL Interval 42.4 to 95.4
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 16	65.8 ng/mL Interval 47.1 to 91.9	73.1 ng/mL Interval 49.1 to 92.7
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 22	49.0 ng/mL Interval 33.3 to 97.1	41.2 ng/mL Interval 41.2 to 41.2
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 34	50.2 ng/mL Interval to 110.0 below lower limit of quantification (0.25 ng/mL)	34.8 ng/mL Interval 34.8 to 34.8
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 46	59.5 ng/mL Interval 49.4 to 66.4	33.5 ng/mL Interval 23.3 to 43.7
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 58	87.0 ng/mL Interval 51.9 to 122.0	—
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 70	56.4 ng/mL Interval 56.4 to 56.4	—
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 82	65.9 ng/mL Interval 65.9 to 65.9	—
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 94	64.2 ng/mL Interval 64.2 to 64.2	—
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Week 106	83.5 ng/mL Interval 83.5 to 83.5	—
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time Safety Follow-Up	NA ng/mL Interval to 2.14 below lower limit of quantification (0.25 ng/mL)	—

SECONDARY outcome

Timeframe: Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=9 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=7 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 4	22.8 ng/mL Interval 11.6 to 29.4	29.2 ng/mL Interval 16.5 to 43.4
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 7	1.21 ng/mL Interval 0.582 to 3.89	1.71 ng/mL Interval 0.405 to 3.22
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 10	19.2 ng/mL Interval 14.0 to 40.6	21.5 ng/mL Interval 18.0 to 41.3
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 16	19.3 ng/mL Interval 13.7 to 22.7	22.0 ng/mL Interval 21.6 to 40.5
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 22	12.7 ng/mL Interval 10.1 to 28.5	18.7 ng/mL Interval 18.7 to 18.7
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 34	18.3 ng/mL Interval to 38.3 below lower limit of quantification (0.25 ng/mL)	15.0 ng/mL Interval 15.0 to 15.0
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 46	15.0 ng/mL Interval 10.3 to 23.1	10.6 ng/mL Interval 7.87 to 13.4
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 58	25.7 ng/mL Interval 20.1 to 31.2	—
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 70	22.4 ng/mL Interval 22.4 to 22.4	—
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 82	25.4 ng/mL Interval 25.4 to 25.4	—
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 94	22.1 ng/mL Interval 22.1 to 22.1	—
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Week 106	32.4 ng/mL Interval 32.4 to 32.4	—
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time Safety Follow-Up	0.138 ng/mL Interval to 1.15 below lower limit of quantification (0.25 ng/mL)	—

SECONDARY outcome

Timeframe: 48 months after LSE

Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with a post-baseline result and a negative result or no result at baseline.

Transient positive results were defined as a positive post-baseline result followed by a negative result at the participant's last time point tested within the study period.

Outcome measures

Outcome measures
Measure	Trebananib 10 mg/kg + Sunitinib n=41 Participants Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off	Trebananib 15 mg/kg + Sunitinib n=41 Participants Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline Binding Antibody Positive Post-Baseline (PBL)	0 participants	0 participants
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline Binding Antibody Positive PBL, Transient	0 participants	0 participants
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline Neutralizing Antibody Positive PBL	0 participants	0 participants
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline Neutralizing Antibody Positive PBL, Transient	0 participants	0 participants

Adverse Events

Trebananib 10 mg/kg + Sunitinib

Serious events: 17 serious events

Other events: 43 other events

Deaths: 0 deaths

Trebananib 15 mg/kg + Sunitinib

Serious events: 26 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER