Prostate Cancer
Conditions
Interventions
- Experimental: Part 1: AMG 509 Intravenous (IV) Monotherapy
Part 1 will evaluate AMG 509 in participants with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated
Neuenschwander et al, 2008).
Recommended phase 2 dose (RP2D) may be identified based on emerging safety, efficacy, PK, and pharmacodynamics (PD) data, as well as patient experience prior to reaching a
Sponsors
Tagashira Shuzo
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Parts 1, 2, 5 and 7: Participants with histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC) who are refractory to a novel antiandrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, or darolutamide) and have failed at least 1 (but not more than 2) taxane regimens including for metastatic hormone-sensitive prostate cancer (mHSPC) (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Note: A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Any NHT that has been administered and has been stopped for reasons other than progression will not be counted as an additional line of treatment. 1. Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease. 2. Dose-expansion phase: participants must not have had more than 2 NHTs and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-PD1, PARP inhibitors, radioligand therapies, sipuleucel-T, experimental agents) Note: Combinations are considered one systemic anti-cancer treatment. - Part 3: Participants with histologically or cytologically confirmed mCRPC who have received no or 1-2 prior NHTs (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen (unless taxane treatment was administered in HSPC setting). 0 1 prior PARP inhibitors or sipuleucel-T treatments are acceptable. Participants who received prior investigational therapy for the treatment of metastatic disease are not eligible. - Parts 4A, 4B and 7: 1. Participants with histologically or cytologically confirmed mCRPC who have received no or 1-2 prior NHTs (given in any disease setting depending on the part), and no or 1 taxane regimen (for HSPC). 2. Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable. 3. Part 4A: Participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible). Participants may have had exposure to up to 2 NHTs with a similar mechanism of action (apalutamide, enzalutamide or darolutamide) in the non-mCRPC and mCRPC setting. - Dose-expansion phase: up to approximately 10participants with prior exposure to abiraterone acetate may be enrolled into Part 4A expansion cohort. d. Part 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible). - Part 6: 1. Prior disease progression on 1, and only 1, NHT(either enzalutamide, apalutamide, or darolutamide) is required. NOTE: Prior progression on or intolerance to abiraterone is not allowed. 2. No prior treatment with any chemotherapy regimen in the mCRPC setting; = 1 RECIST v1.1 measurable lesion that is present on baseline computed tomography (CT) or magnetic resonance imaging (MRI). - All parts: - Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonis tor antagonist. - Total serum testosterone <= 50 ng/dL or 1.7
Exclusion criteria
Exclusion criteria: - Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma - Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose) - Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. - Prior major surgery within 4 weeks of first dose. - Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration. NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with sponsor. Screening for chronic infectious conditions is not required. - Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy - History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of AMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation. NOTE: Participants with a recent history of venous thrombosis must be maintained on the same anti-coagulation therapy for a minimum of 28 days prior to first dose of study treatment. - Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509 with the exception of ischemia or non-ST segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of AMG 509. - Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist/antagonist). - Prior prostate specific membrane antigen (PSMA) radionuclide therapy within 2 months prior to AMG 509 unless participant received = 30 days prior to enrollment are eligible (exception: part 3 additional course of treatment). - Part 3 - additional course of treatment only: Any anti-cancer therapy or immunotherapy, not including luteinizing hormone-releasing hormone/gonadotropin releasing hormone (LHRH/GnRH) analogue (agonist/antagonist), and/or bisphosphonate or denosumab regimen after last dose of AMG 509 initial course of treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Parts 1-5 and 7: Incidence of Treatment-emergent Adverse Events [Time Frame: 3 years] 2. Parts 1-5 and 7: Incidence of Treatment-related Adverse Events [Time Frame: 3 years] 3. Parts 1-5 and 7 Dose Exploration Cohorts Only: Dose Limiting Toxicities (DLTs) [Time Frame:28 days] 4. Parts 1-5 and 7: Number of Participants with Changes in Vital Signs [Time Frame: 3 years] 5. Parts 1-5 and 7: Number of Participants with Changes in Electrocardiogram (ECG) Records [Time Frame: 3 years] 6. Parts 1-5 and 7: Number of Participants with Changes in Clinical Laboratory Test Results [Time Frame: 3 years] 7. Part 6: Objective Response (OR) per RECIST v1.1 [Time Frame: 3 years] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Parts 1-7: Maximum Serum Concentration (Cmax) for AMG 509 [Time Frame: 3 years] To characterize the pharmacokinetics (PK) of AMG 509 2. Parts 1-7: Time to Maximum Serum Concentration (Tmax) for AMG 509 [Time Frame: 3years] To characterize the pharmacokinetics (PK) of AMG 509 3. Parts 1-7: Minimum Serum Concentration (Cmin) for AMG 509 [Time Frame: 3 years] To characterize the pharmacokinetics (PK) of AMG 509 4. Parts 1-7: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval for AMG509 [Time Frame: 3 years] To characterize the pharmacokinetics (PK) of AMG 509 5. Parts 1-7: Accumulation Following Multiple Dosing for AMG 509 [Time Frame: 3 years] To characterize the pharmacokinetics (PK) of AMG 509 6. Parts 1-5 and 7: OR per RECIST v1.1 [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 7. Parts 1-7: Prostate Specific Antigen (PSA) Response [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 8. Parts 1-5 and 7: PSA Decline of at Least 50% From Baseline at 12 Weeks [Time Frame: Week12] To evaluate preliminary anti-tumor activity of AMG 509 9. Parts 1-7: Radiographic Duration of Response (DOR) [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 10. Parts 1-5 and 7: PSA DOR [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 11. Parts 1-5 and 7: Radiographic Time to Progression [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 12. Parts 1-5 and 7: PSA Time to Progression [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 13. Parts 1-5 and 7: Radiographic Progression-free Survival (PFS) [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 14. Parts 1-5 and 7: PSA PFS [Time Frame: 3 years] To evaluate preliminary anti-tumor activity of AMG 509 15. Part 6: Radiographic PFS per Prostate Cancer Working Group 3 (PCWG3)-modified RECISTv1.1 [Time Frame: 3 years] To eval | — |
Countries
Australia, China, Germany, Japan, Portugal, South Korea, Spain, Switzerland, Taiwan, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed