Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Trebananib
Amgen 386 · 3 trials · 18 indications
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).
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.
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.
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).
PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010). RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown status. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: \>= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non- enhancing lesions, and stable or improved clinically. PD: \> 25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: d
The MTD of weekly AMG 386 intravenously (IV) in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1 and 15 of each 28 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached but the highest dose received may be the Recommended Phase II Dose (RP2D).
A DLT is defined as an adverse event that (a) is related to the AMG 386 and/or bevacizumab with an attribution of possible, probable, or definite, and (b) occurs during and/or begins during the first 28 days of the study treatment, and (c) meets any of the following criteria: \>= grade 3 thrombocytopenia; grade 4 neutropenia lasting \> 7 days; grade 4 anemia lasting \> 7 days despite transfusion or growth factors; febrile neutropenia if ANC\<0.5x10\^9/L; clinically significant grade 3 non-hematologic toxicity despite maximal medical therapy lasting \> 7 days, with the exception of grade 3 proteinuria which was considered a DLT if lasting \> 14 days; grade 3 non-hematologic toxicity resulting in study drug discontinuation; grade 4 non-hematologic toxicity; \>= grade 1 new CNS hemorrhage; \>= grade 2 non-CNS hemorrhage.
Adverse events will be tabulated overall and by arm.
A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual areas-under-the-curve (AUCs) and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.
A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual AUCs and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.
| Arm | Type | Description |
|---|---|---|
| Trebananib 10 mg/kg + Sunitinib | EXPERIMENTAL | 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 | EXPERIMENTAL | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Amgen 386 | EXPERIMENTAL | Cohort A will assess recurrent Glioblastoma Multiforme (GBM) patients who receive AMG 386 monotherapy at 30mg/kg every week. As of August 1, 2013, Cohort A was closed to new accrual following early interim analysis of first 10 participants enrolled on study. None of these patients had achieved stable disease or response at their initial evaluation after 1-2 months of study therapy. Therefore, study investigators and sponsor agreed that the level of single-agent anti-tumor activity associated with AMG386 for recurrent glioblastoma patients is most likely insufficient to satisfy the stopping rule for low efficacy outlined in Section 14.5 for Cohort A. |
| Amgen 386 and Bevacizumab | EXPERIMENTAL | Cohort B will assess recurrent Glioblastoma Multiforme(GBM) patients who receive AMG 386 plus bevacizumab. Because the maximum tolerated dose of this combination therapy has not yet been established, a 3x3 Phase I study was used to determine the maximum tolerated dose. As of June 6, 2014, the MTD was determined to be AMG386 30 mg/kg administered intravenously every week(dose level +1) in combination with bevacizumab at 10mg/kg administered intravenously every other week. As of July 25, 2014 the Cohort B, Phase II portion of the study was opened to accrual. |
| Arm A (trebananib) | EXPERIMENTAL | Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. |
| Arm B (trebananib, cytarabine) | EXPERIMENTAL | Patients receive trebananib as in Arm A. Patients also receive cytarabine SC BID on days 1-14 of course 1 and days 1-7 of subsequent courses. |
| Name | Type | Description |
|---|---|---|
| Sunitinib | DRUG | 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. |
| Trebananib | DRUG | Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death. |
| Amgen 386 | DRUG | For Cohort A, AMG 386 will be administered intravenously at 30 mg/kg every week. For Cohort B Phase I, AMG 386 will be administered intravenously at beginning at starting dose level of 15 mg/kg every week. For Cohort B Phase II, AMG 386 will be administered intravenously at the maximum tolerated dose determined in the Phase I portion of the study every week. |
| Bevacizumab | DRUG | The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other week. |
| cytarabine | DRUG | Given SC |
| laboratory biomarker analysis | OTHER | Correlative studies |
| pharmacological study | OTHER | Correlative studies |
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 unidime...
Amgen 386 is an investigational small molecule being studied for glioblastoma multiforme, a type of brain cancer. It was evaluated in a Phase 1 trial in adults with recurrent glioblastoma. It is not an approved therapy and remains in clinical development.
Amgen 386 is being developed by Amgen Inc., which trades on Nasdaq under the ticker AMGN. Amgen sponsored the Phase 1 study of the compound in recurrent glioblastoma conducted in the United States.
Amgen 386 is in Phase 1 development. One Phase 1 trial has been completed, and no active trials are currently listed. The study enrolled 48 participants and was conducted in the United States.
Amgen 386 has been studied in one clinical trial, NCT01290263, titled Amgen 386 for Recurrent Glioblastoma. That Phase 1 trial is completed, enrolled 48 adults aged 18 years and older, and was conducted in the United States.
Amgen 386 is not approved. It is an investigational small molecule that has completed a Phase 1 trial in recurrent glioblastoma multiforme. No regulatory approval has been granted for this compound.
The Amgen 386 Phase 1 trial, NCT01290263, was a controlled study but was not randomized and not double blinded. It enrolled 48 participants with recurrent glioblastoma multiforme in the United States and has been completed.