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Also known as Taxol, Angiogenesis inhibitor, Liposomal doxorubicin, Topotecan, Trebananib
AMG 386 · 15 trials · 42 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).
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.
Paclitaxel PK parameters with and without the co-administration of AMG 386.
| Arm | Type | Description |
|---|---|---|
| AMG 386 | EXPERIMENTAL | Arm A: Paclitaxel 80mg/m2 IV QW and Blinded AMG 386 15mg/kg IV QW |
| AMG 386 Placebo | PLACEBO_COMPARATOR | Arm B: Paclitaxel 80mg/m2 IV QW and Blinded AMG 386 Placebo IV QW |
| 15mg/ kg cohort | EXPERIMENTAL | AMG 386 15mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. |
| 10 mg/kg cohort | EXPERIMENTAL | AMG 386 10mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. |
| 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 |
| 2 | PLACEBO_COMPARATOR | AMG 386 placebo QW, FOLFIRI Q2W |
| 1 | ACTIVE_COMPARATOR | Arm 1 : AMG 386 10 mg/kg QW, FOLFIRI Q2W |
| B | EXPERIMENTAL | - |
| A | EXPERIMENTAL | - |
| C | ACTIVE_COMPARATOR | - |
| Arm A | EXPERIMENTAL | Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 10 mg/kg IV QW |
| Arm B | EXPERIMENTAL | Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 3 mg/kg IV QW |
| Arm C | ACTIVE_COMPARATOR | Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 placebo |
| D | EXPERIMENTAL | Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW |
| 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. |
| AMG 386 15mg/kg and paclitaxel 80mg/m2 | EXPERIMENTAL | - |
| Group 1 | EXPERIMENTAL | Cancer subjects with normal renal function. |
| Group 3 | EXPERIMENTAL | Cancer subjects with moderate renal impairment. |
| Group 4 | EXPERIMENTAL | Cancer subjects with severe renal impairment. |
| Group 2 | EXPERIMENTAL | Cancer subjects with mild renal impairment. |
| AMG 386, paclitaxel and carboplatin | EXPERIMENTAL | 15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months. |
| Cohort A1 | EXPERIMENTAL | - |
| Cohort A3 | EXPERIMENTAL | - |
| Cohort B1 | EXPERIMENTAL | - |
| Cohort B3 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AMG 386 | DRUG | Weekly Intravenous (IV) AMG 386 15 mg/kg |
| AMG 386 Placebo | DRUG | Weekly Intravenous (IV) placebo 15 mg/kg |
| Paclitaxel | DRUG | Paclitaxel 80 mg/m2 intravenous (IV) weekly (3 on/1 off) |
| Sorafenib | DRUG | Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort \& 10mg/kg cohort |
| 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. |
| FOLFIRI | DRUG | Administration of FOLFIRI chemotherapy will commence on day 1 of each dosing week following the administration of AMG 386. FOLFIRI Q2W regimen: irinotecan 180 mg/m2 IV over 90 (+-15) minutes on Day 1, leucovorin 400 mg/m2 IV over 2 hrs on Day 1, 5 FU 400mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hrs +- 2 hours. FOLFIRI will be administered until disease progression, FOLFIRI intolerability, death, or study withdrawal by the subject, investigator, or sponsor, whichever occurs earliest. |
| AMG 386 10mg/kg | DRUG | AMG 386 10 mg/kg IV QW until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death |
| AMG 386 3mg/kg | DRUG | AMG 386 3 mg/kg IV QW until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death |
| Cisplatin | DRUG | Cisplatin 80 mg/m2 IV Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death |
| Capecitabine | DRUG | Capecitabine1000 mg/m2 PO BID x 14 days Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death |
| Bevacizumab | DRUG | Bevacizumab 10mg/kg IV Q2W |
| AMG 386 placebo IV | DRUG | AMG 386 placebo IV |
| cytarabine | DRUG | Given SC |
| laboratory biomarker analysis | OTHER | Correlative studies |
| pharmacological study | OTHER | Correlative studies |
| Pemetrexed | DRUG | Pemetrexed 500 mg/m2 |
| Carboplatin | DRUG | Carboplatin AUC 6 |
| AMG 386 + Paclitaxel | DRUG | 15 mg/kg IV (in the vein) of AMG 386 weekly + 80 mg/m\^2 IV (in the vein) 3 weeks on/1 week off, optional beginning week 6 until progression, unacceptable toxicity, or withdrawal of consent. |
| AMG 386, paclitaxel and carboplatin | DRUG | 15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months. |
| AMG 386 30 mg/kg, Paclitaxel and Trastuzumab | DRUG | AMG 386 30 mg/kg IV QW, paclitaxel 80 mg/m2 IV QW, trastuzumab: initial dose 8 mg/kg IV week 1, then 6 mg/kg IV Q3W |
| AMG 386 30 mg/kg, Capecitabine and Lapatinib | DRUG | AMG 386 30 mg/kg IV QW, capecitabine 2000 mg/m2 divided into 2 doses given PO Q12 hrs, days 1-14 every 21 days, lapatinib 1250 mg PO QD |
| AMG 386 10 mgkg, Paclitaxel and Trastuzumab | DRUG | AMG 386 10 mg/kg IV QW, paclitaxel 80 mg/m2 IV QW, trastuzumab: initial dose 8 mg/kg IV week 1, then 6 mg/kg IV Q3W |
| AMG 386 10 mg/kg, Capecitabine and Lapatinib | DRUG | AMG 386 10 mg/kg IV QW, capecitabine 2000 mg/m2 divided into 2 doses given PO Q12 hrs, days 1-14 every 21 days, lapatinib 1250 mg PO QD |
Inclusion Criteria: * Female 18 years of age or older at the time the written informed consent is obtained * Gynecologic Oncology Group (GOG) Performance Status of 0 or 1 * Life expectancy \>= 3 months (per investigator opinion) * Histologically or cytologically documented invasive epithelial ovari...
AMG 386 is an investigational oncology drug developed by Amgen Inc. (ticker AMGN). It has been studied in advanced solid tumors, breast cancer, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, and non-small cell lung cancer. It is a small molecule agent that has been evaluated in Phase 2 clinical development, primarily in combination with chemotherapy agents such as paclitaxel and carboplatin.
AMG 386 is developed by Amgen Inc., which trades under the ticker AMGN. Amgen sponsored the clinical trials evaluating AMG 386 in advanced solid tumors, ovarian cancer, non-small cell lung cancer, and other cancer types. The drug has been studied both as a single agent and in combination with chemotherapy regimens including paclitaxel, carboplatin, and pemetrexed.
AMG 386 is in Phase 2 development. It is an investigational agent and has not been approved by the FDA. Clinical trials of AMG 386 have been completed, including Phase 1 and Phase 1b/2 studies, with no active trials currently ongoing. The completed studies enrolled a total of 919 participants across multiple cancer indications.
AMG 386 has been evaluated in completed clinical trials including NCT01992341, a Phase 1 drug-drug interaction study with paclitaxel in advanced solid tumors; NCT01666977, a Phase 1b/2 trial with pemetrexed and carboplatin in non-small cell lung cancer; NCT01331941, a pharmacokinetic study in cancer subjects with normal and impaired renal function; and NCT01253681, a Phase 1 study with paclitaxel and carboplatin in ovarian cancer.
AMG 386 has been studied for the treatment of advanced hepatocellular carcinoma, advanced renal cell carcinoma, advanced solid tumors, breast cancer, and carcinoma. It has also been evaluated in ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and non-small cell lung cancer. All studies of AMG 386 have been completed, and the drug remains investigational.