Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT04221542
- Lead Sponsor
- Amgen
- Brief Summary
Evaluate the safety and tolerability of AMG 509 in adult participants and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Part 2 is now closed to accrual.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 470
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Parts 1, 2, and 5: 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.
- Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.
- 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.
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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. Subjects who received prior investigational therapy for the treatment of metastatic disease are not eligible.
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Parts 4A and 4B:
- 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).
- Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable.
- 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.
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Dose expansion phase: up to approximately 10 subjects with prior exposure to abiraterone acetate may be enrolled into Part 4A expansion cohort.
d. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
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All parts:
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Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist.
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Total serum testosterone <= 50 ng/dL or 1.7 nmol/L.
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Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria:
- PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
- Nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications.
- Appearance of 2 or more new lesions in bone scan.
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Eastern Cooperative Oncology Group performance status of 0-1.
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Adequate organ function, defined as follows:
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Hematological function:
- absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment).
- platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment).
- hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).
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Renal function:
- estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation >= 30 ml/min/1.73 m^2.
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Hepatic function:
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement).
- total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases).
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Cardiac function:
- left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available).
- Baseline electrocardiogram (ECG) QTcF <= 470 msec (average of triplicate values).
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Part 3-Retreatment group:
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Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following:
- confirmed PSA50 response.
- radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with AMG 509 and without progression during the first 6 cycles.
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No discontinuation for toxicity during the initial treatment with 6 cycles of AMG 509.
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Progressive disease as defined in I106 within 12 months of final dose in their initial treatment with 6 cycles (EOT_1).
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Willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator.
- 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.
- 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.
- 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.
- 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 anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist/antagonist).
- Prior PSMA radionuclide therapy within 2 months prior to AMG 509 unless participant received < 2 cycles (Note: a participant cannot have received PSMA radionuclide therapy < 35 days prior to enrollment if 1 cycle was given). Parts 3 and 4: prior PSMA radionuclide therapy is prohibited. Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible (exception: part 3 retreatment).
- Part 3-Retreatment only: Any anticancer 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: AMG 509 Subcutaneous (SC) Monotherapy AMG 509 Part 2 will explore the safety, tolerability, and PK of AMG 509 SC dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes. Recommended phase 2 dose for SC monotherapy may be identified based on emerging safety, efficacy, PK, and PD data, as well as patient experience prior to reaching an MTD. Part 4: AMG 509 IV Combination Therapy Abiraterone Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 0/2 prior NHT (for hormone sensitive or castration-resistant disease) at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A), or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B. Part 4 consists of a dose exploration phase and a dose expansion phase. This dose exploration study will estimate the MTD and/or RP2D of AMG 509 in combination with abiraterone or enzalutamide using a modified toxicity probability interval design. The dose-expansion phase will confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and correlative biomarker analysis. Part 4: AMG 509 IV Combination Therapy Enzalutamide Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 0/2 prior NHT (for hormone sensitive or castration-resistant disease) at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A), or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B. Part 4 consists of a dose exploration phase and a dose expansion phase. This dose exploration study will estimate the MTD and/or RP2D of AMG 509 in combination with abiraterone or enzalutamide using a modified toxicity probability interval design. The dose-expansion phase will confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and correlative biomarker analysis. Part 5: AMG 509 IV Monotherapy in Outpatient Setting AMG 509 Part 5 will evaluate the safety and tolerability of AMG 509 IV dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes, when administered in outpatient infusion centers. The Part 5 dosing regimen and schedule was selected based on emerging data and DLRT recommendations and will utilize the doses explored in Part 1 dose-expansion phase Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment AMG 509 Part 3 will explore AMG 509 in participants with mCRPC who have received no, or 1-2 prior NHTs (may have been given for HSPC) and no prior taxanes (unless administered in HSPC setting). This dose expansion will be conducted to confirm safety, PK, and PD of AMG 509 at the MTD or RP2D determined in Part 1 dose exploration, and to obtain further safety and efficacy data and correlative biomarker analysis. Part 4: AMG 509 IV Combination Therapy AMG 509 Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 0/2 prior NHT (for hormone sensitive or castration-resistant disease) at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A), or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B. Part 4 consists of a dose exploration phase and a dose expansion phase. This dose exploration study will estimate the MTD and/or RP2D of AMG 509 in combination with abiraterone or enzalutamide using a modified toxicity probability interval design. The dose-expansion phase will confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and correlative biomarker analysis. Part 1: AMG 509 Intravenous (IV) Monotherapy AMG 509 Part 1 will evaluate AMG 509 in participants with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with novel hormonal therapy (NHT) and 1 to 2 prior taxanes. The dose exploration phase of the study will estimate the MTD of AMG 509 using a Bayesian logistic regression model (BLRM; Neuenschwander et al, 2008). RP2D may be identified based on emerging safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) data, as well as patient experience prior to reaching an MTD. Alternative dosing schedule(s) (including a third step dose) may be explored based on emerging efficacy, safety, PK data and patient experience. During the dose expansion phase, individual cohorts of participants from China will be enrolled with a safety lead-in at 1 dose level below the MTD or RP2D followed by evaluation at the MTD or RP2D to confirm the safety, tolerability, MTD and/or RP2D of AMG 509 in Chinese participants.
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events 3 years Dose limiting toxicities (DLTs) 3 years Number of participants with changes in vital signs 3 years Number of participants with changes in the electrocardiogram (ECG) records 3 years Number of participants with changes in the clinical laboratory tests results 3 years Incidence of treatment-related adverse events 3 years
- Secondary Outcome Measures
Name Time Method 1, 2, and 3-year overall survival (OS) Year 1, 2, and 3 To evaluate preliminary anti-tumor activity of AMG 509
Maximum serum concentration (Cmax) for AMG 509 3 years To characterize the pharmacokinetics (PK) of AMG 509
Minimum serum concentration (Cmin) for AMG 509 3 years To characterize the pharmacokinetics (PK) of AMG 509
Accumulation following multiple dosing for AMG 509 3 years To characterize the pharmacokinetics (PK) of AMG 509
Lactate dehydrogenase (LDH) 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Area under the concentration-time curve (AUC) over the dosing interval for AMG 509 3 years To characterize the pharmacokinetics (PK) of AMG 509
Progression-free survival (PFS) (radiographic and PSA) 3 years To evaluate preliminary anti-tumor activity of AMG 509
6 month radiographic PFS 6 months To evaluate preliminary anti-tumor activity of AMG 509
Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications 3 years To evaluate preliminary anti-tumor activity of AMG 509
Prostate specific antigen (PSA) response 3 years To evaluate preliminary anti-tumor activity of AMG 509
Alkaline phosphatase (total, bone) 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Time to maximum serum concentration (Tmax) for AMG 509 3 years To characterize the pharmacokinetics (PK) of AMG 509
PSA decline of at least 50% from baseline at 12 weeks Week 12 To evaluate preliminary anti-tumor activity of AMG 509
Duration of response (DOR) (radiographic and PSA) 3 years To evaluate preliminary anti-tumor activity of AMG 509
1, 2, and 3-year radiographic PFS Year 1, 2, and 3 To evaluate preliminary anti-tumor activity of AMG 509
Circulating tumor cells response (CTC0) 3 years To evaluate preliminary anti-tumor activity of AMG 509
Rate of circulating tumor cells (CTC) conversion 3 years To evaluate preliminary anti-tumor activity of AMG 509
Time to progression (radiographic and PSA) 3 years To evaluate preliminary anti-tumor activity of AMG 509
Time to symptomatic skeletal events 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Hemoglobin 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Neutrophil-to-lymphocyte ratio 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Urine N-telopeptide 3 years To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Trial Locations
- Locations (54)
HOCH Health Ostschweiz
🇨🇭Sankt Gallen, Switzerland
United States Oncology Regulatory Affairs Corporate Office
🇺🇸Nashville, Tennessee, United States
US Oncology Research Investigational Products Center
🇺🇸Irving, Texas, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Providence Saint Jude Medical Center
🇺🇸Fullerton, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Alliance for Multispecialty Research
🇺🇸Merriam, Kansas, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Oncology Hematology Care Incorporated
🇺🇸Cincinnati, Ohio, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health Upstate
🇺🇸Greenville, South Carolina, United States
Sanford Oncology Clinic and Pharmacy
🇺🇸Sioux Falls, South Dakota, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Virginia Cancer Specialists PC
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Chris OBrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Sun Yat-sen University, Cancer Center
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Fudan University Shanghai Cancer Centre
🇨🇳Shanghai, Shanghai, China
Zhejiang Provincial Peoples Hospital
🇨🇳Hangzhou, Zhejiang, China
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Klinikum rechts der Isar der TUM
🇩🇪Muenchen, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
Yokohama City University Hospital
🇯🇵Yokohama-shi, Kanagawa, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵Koto-ku, Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital da Luz, SA
🇵🇹Lisboa, Portugal
Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
🇵🇹Porto, Portugal
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Cataluña, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Cataluña, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Istituto Oncologico della Svizzera Italiana
🇨🇭Bellinzona, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
🇨🇳Taoyuan, Taiwan