Advanced Renal Cell Carcinoma
Conditions
Brief summary
This phase 2 study is an open-label, multi-center study to determine the safety and tolerability of AMG 386 in combination with sunitinib in the treatment of subjects with metastatic renal cell carcinoma.
Interventions
DRUGSunitinib
Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of reneal cell cancer (RCC) and will be administered to all participants.
DRUGTrebananib
Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have a histologically confirmed metastatic renal cell cancer (RCC) with a clear cell component * Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification * Measurable disease with at least one unidimensionally measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) guidelines with modifications * Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening * Eastern Cooperative Oncology Group (ECOG) of 0 or 1
Exclusion criteria
Disease related * Known history of central nervous system metastases. * Previous treatment (excluding surgery, prior cytokine-based immunotherapy and palliative radiotherapy) for advanced or metastatic renal cell carcinoma * Focal radiation therapy for palliation of pain from bony metastases within 14 days of enrollment. Medications * Currently or previously treated with sunitinib or other small molecule inhibitors of vascular endothelial growth factor (VEGF) * Currently or previously treated with agents that neutralizing VEGF * Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor * Currently or previously treated with agents inhibiting the mammalian target of rapamycin (mTOR) * Current or within 30 days prior to enrollment treatment with immune modulators * Concomitant or previous use within 30 days prior to enrollment of any strong inducer of CYP3A4 * Concomitant or previous use of amiodarone within 6 months prior to enrollment General medical * Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent * Major surgery within 28 days prior to enrollment or still recovering from prior surgery * Uncontrolled hypertension as defined as diastolic \> 90 mmHg OR systolic \>150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted. Other * Other investigational procedures are excluded * Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | 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. | 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). |
| Number of Participants With Dose Delays Due to Adverse Events | 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. | 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. |
| Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | first 12 weeks of study treatment | 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. |
| Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | 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. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate: Overall Survival (OS) | 48 months after LSE | 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. |
| Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir | Baseline, 48 months after LSE | Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions. |
| Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | 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) | — |
| Objective Response Rate (ORR) | 48 months after last subject enrolled (LSE) | 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. |
| Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | 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) | — |
| Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | 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) | — |
| Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | 48 months after LSE | 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. |
| Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | 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) | — |
| Kaplan-Meier Estimate: Duration of Response (DOR) | 48 months after LSE | 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. |
| Disease Control Rate (DCR) | 48 months after LSE | 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. |
| Kaplan-Meier Estimate: Progression Free Survival (PFS) | 48 months after LSE | 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. |
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Trebananib 10 mg/kg + Sunitinib Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | 43 |
| Trebananib 15 mg/kg + Sunitinib Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | 42 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 30 | 26 |
| Overall Study | Full Consent Withdrawn | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Trebananib 10 mg/kg + Sunitinib | Total | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|---|
| Age, Customized < 65 years | 30 participants | 57 participants | 27 participants |
| Age, Customized >= 65 years | 13 participants | 28 participants | 15 participants |
| Age, Customized < 75 years | 41 participants | 81 participants | 40 participants |
| Age, Customized >= 75 years | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Aborigine | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Japanese | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other, Not Specified | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White or Caucasian | 41 participants | 83 participants | 42 participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 10 Participants |
| Sex: Female, Male Male | 38 Participants | 70 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 43 | 42 / 42 |
| serious Total, serious adverse events | 17 / 43 | 26 / 42 |
Outcome results
Primary
Number of Participants With Dose Delays Due to Adverse Events
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Dose Delays Due to Adverse Events | Trebananib Dose Delays | 26 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Dose Delays Due to Adverse Events | Sunitinib Dose Delays | 29 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Dose Delays Due to Adverse Events | Trebananib Dose Delays | 28 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Dose Delays Due to Adverse Events | Sunitinib Dose Delays | 27 participants |
Primary
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Laboratory Toxicity | 4 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | Any Dose Modification (DM) | 25 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Laboratory Toxicity and Adverse Event | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Adverse Event | 20 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Laboratory Toxicity and Adverse Event | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Adverse Event | 18 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | Any Dose Modification (DM) | 24 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose | DM Due to Laboratory Toxicity | 4 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 31 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TEAEs, Grade ≥ 4 | 7 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TEAEs, SAEs | 26 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 12 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 14 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | SR TEAEs, SAEs | 15 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 10 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TEAEs, All | 42 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 14 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 16 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 12 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 12 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 42 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 31 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 10 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 10 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TR TEAEs, SAEs | 18 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | 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 | 15 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 39 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 19 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 4 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TrR TEAEs, SAEs | 15 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 3 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 13 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 11 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | 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 | 42 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) | TEAEs, Grade ≥ 3 | 34 participants |
Primary
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values
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).
Time frame: 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 Aanalysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Alkaline Phosphatase, AN | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Potassium, BN | 2 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Alanine Aminotransferase, Above Normal (AN) | 3 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Sodium, BN | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Amylase, AN | 2 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Total Bilirubin, AN | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Aspartate Aminotransferase, AN | 2 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Absolute Neutrophil Count, BN | 3 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Glucose, BN | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Hemoglobin, BN | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Lipase, AN | 5 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Lymphocytes, BN | 6 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Albumin, Below Normal (BN) | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Partial Thromboplastin Time, AN | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Magnesium, BN | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Platelets, BN | 3 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Glucose, AN | 1 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Total Neutrophils, BN | 3 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Phosphorus, BN | 3 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Total Neutrophils, BN | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Glucose, AN | 3 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Glucose, BN | 0 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Alanine Aminotransferase, Above Normal (AN) | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Albumin, Below Normal (BN) | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Alkaline Phosphatase, AN | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Aspartate Aminotransferase, AN | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Lipase, AN | 7 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Magnesium, BN | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Phosphorus, BN | 4 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Potassium, BN | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Sodium, BN | 4 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Total Bilirubin, AN | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Absolute Neutrophil Count, BN | 5 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Hemoglobin, BN | 3 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Lymphocytes, BN | 3 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Partial Thromboplastin Time, AN | 1 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Platelets, BN | 2 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values | Amylase, AN | 5 participants |
Secondary
Disease Control Rate (DCR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Disease Control Rate (DCR) | 72.1 percentage of participants |
| Trebananib 15 mg/kg + Sunitinib | Disease Control Rate (DCR) | 75.6 percentage of participants |
Secondary
Kaplan-Meier Estimate: Duration of Response (DOR)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Kaplan-Meier Estimate: Duration of Response (DOR) | 18.0 months |
| Trebananib 15 mg/kg + Sunitinib | Kaplan-Meier Estimate: Duration of Response (DOR) | 18.4 months |
Secondary
Kaplan-Meier Estimate: Overall Survival (OS)
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.
Time frame: 48 months after LSE
Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Kaplan-Meier Estimate: Overall Survival (OS) | 36.0 months |
| Trebananib 15 mg/kg + Sunitinib | Kaplan-Meier Estimate: Overall Survival (OS) | 38.7 months |
Secondary
Kaplan-Meier Estimate: Progression Free Survival (PFS)
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.
Time frame: 48 months after LSE
Population: Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Kaplan-Meier Estimate: Progression Free Survival (PFS) | 13.9 months |
| Trebananib 15 mg/kg + Sunitinib | Kaplan-Meier Estimate: Progression Free Survival (PFS) | 16.5 months |
Secondary
Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir
Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | 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 |
| Trebananib 15 mg/kg + Sunitinib | Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir | -41.8 percent reduction in SLD |
Secondary
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Binding Antibody Positive Post-Baseline (PBL) | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Neutralizing Antibody Positive PBL | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Binding Antibody Positive PBL, Transient | 0 participants |
| Trebananib 10 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Neutralizing Antibody Positive PBL, Transient | 0 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Binding Antibody Positive PBL, Transient | 0 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Binding Antibody Positive Post-Baseline (PBL) | 0 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Neutralizing Antibody Positive PBL, Transient | 0 participants |
| Trebananib 15 mg/kg + Sunitinib | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline | Neutralizing Antibody Positive PBL | 0 participants |
Secondary
Objective Response Rate (ORR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Objective Response Rate (ORR) | 58.1 percentage of participants |
| Trebananib 15 mg/kg + Sunitinib | Objective Response Rate (ORR) | 63.4 percentage of participants |
Secondary
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Safety Follow-Up | 0.138 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 46 | 15.0 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 58 | 25.7 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 70 | 22.4 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 82 | 25.4 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 94 | 22.1 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 106 | 32.4 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 4 | 22.8 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 7 | 1.21 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 10 | 19.2 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 16 | 19.3 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 22 | 12.7 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 34 | 18.3 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 4 | 29.2 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 34 | 15.0 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 7 | 1.71 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 22 | 18.7 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 10 | 21.5 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 46 | 10.6 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time | Week 16 | 22.0 ng/mL |
Secondary
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Safety Follow-Up | NA ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 46 | 59.5 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 58 | 87.0 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 70 | 56.4 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 82 | 65.9 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 94 | 64.2 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 106 | 83.5 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 4 | 58.6 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 7 | 0.763 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 10 | 66.1 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 16 | 65.8 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 22 | 49.0 ng/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 34 | 50.2 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 4 | 70.6 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 34 | 34.8 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 7 | 1.65 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 22 | 41.2 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 10 | 64.7 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 46 | 33.5 ng/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time | Week 16 | 73.1 ng/mL |
Secondary
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 46 | 221 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 13 | 219 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 58 | 229 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 70 | 185 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 82 | 223 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 94 | 270 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 106 | 289 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Safety Follow-Up | 3.46 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 1 | 222 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 4 | 285 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 22 | 249 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 10 | 257 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 34 | 240 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 7 | 260 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Safety Follow-Up | 8.26 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 1 | 297 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 4 | 377 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 7 | 377 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 10 | 476 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 13 | 385 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 22 | 417 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 34 | 387 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time | Week 46 | 349 µg/mL |
Secondary
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 4 | 20.4 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 34 | 24.1 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 46 | 23.2 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 58 | 27.9 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 70 | 26.2 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 82 | 22.5 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 94 | 25.9 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 106 | 19.3 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Safety Follow-Up | 3.46 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 7 | 30.1 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 10 | 23.3 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 13 | 26.1 µg/mL |
| Trebananib 10 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 22 | 19.9 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 4 | 27.3 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 22 | 46.2 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 7 | 42.0 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 46 | 30.5 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 10 | 32.2 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 34 | 35.9 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Week 13 | 43.2 µg/mL |
| Trebananib 15 mg/kg + Sunitinib | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time | Safety Follow-Up | 8.26 µg/mL |