Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer
NCT ID: NCT04221542
Last Updated: 2026-01-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
479 participants
INTERVENTIONAL
2020-03-04
2032-03-21
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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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 with novel hormonal therapy (NHT) and 1 to 2 prior taxanes.
The dose exploration phase of the study will estimate the maximum tolerated dose (MTD) of AMG 509 using a Bayesian logistic regression model (BLRM; 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 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.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Part 2: AMG 509 Subcutaneous (SC) Monotherapy
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.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment
Part 3 will explore AMG 509 in participants with mCRPC who have received no, or 1-2 prior NHTs (may have been given for hormone-sensitive prostate cancer \[HSPC\]) 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.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Part 4: AMG 509 IV Combination Therapy
Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 1 to 2 prior NHTs given in any disease setting depending on the part (dose-expansion phase: prior therapies including at least 1 prior NHT and either 0 or 1 prior poly-ADP ribose polymerase \[PARP\] inhibitor), at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone acetate (Part 4A) or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Abiraterone
Abiraterone administered as oral tablets.
Enzalutamide
Enzalutamide administered as oral tablets.
Part 5: AMG 509 IV Monotherapy in Outpatient Setting
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 dose level review team (DLRT) recommendations and will utilize the doses explored in Part 1 dose-expansion phase.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate
Part 6 will evaluate the preliminary efficacy, safety, tolerability, and PK of AMG 509 (alone or in combination with abiraterone acetate) for participants with mCRPC who have progressed on only 1 prior NHT (prior exposure to ≤ 6 cycles of taxane is allowed in mHSPC setting) and who have Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measurable disease.
Part 6 dosing regimen has been previously determined as safe and tolerable and is aligned with the dosing schedule for Parts 3 and 4A expansion.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Abiraterone
Abiraterone administered as oral tablets.
Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate
Part 7 will only include participants from China. This part will evaluate safety and tolerability of AMG 509 IV dosing in participants who have been previously treated with NHT and 1 to 2 prior taxanes.
Part 7 dosing regime will first be enrolled to dose level-1 (1.0 mg target dose) and if tolerated and if DLRT determines it is safe to escalate to the MTD/RP2D, 1.5 mg every 2 weeks (Q2W) dosing regimen may be explored. If the RP2D is safe and tolerable and once AMG 509 monotherapy dose confirmation is complete, a cohort of participants to receive AMG 509 combination therapy with abiraterone acetate may be initiated.
AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Abiraterone
Abiraterone administered as oral tablets.
Interventions
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AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
Abiraterone
Abiraterone administered as oral tablets.
Enzalutamide
Enzalutamide administered as oral tablets.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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. 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 10 participants 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).
* 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; ≤ 6 cycles of docetaxel treatment in the mHSPC setting is allowed.
3. mCRPC with ≥ 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) agonist or antagonist.
* Total serum testosterone ≤ 50 ng/dL or 1.7 nmol/L.
* Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria:
1. PSA level ≥ 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
2. Nodal or visceral progression as defined by RECIST v1.1 with PCGW3 modifications.
3. Appearance of 2 or more new lesions in bone scan.
* Eastern Cooperative Oncology Group performance status of 0-1.
* Life expectancy ≥ 3 months.
* Adequate organ function, defined as follows:
1. Hematological function:
1. absolute neutrophil count ≥ 1 x 10\^9/L (without growth factor support within 7 days from screening assessment).
2. platelet count ≥ 75 x 10\^9/L (without platelet transfusion within 7 days from screening assessment).
3. hemoglobin ≥ 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).
2. Renal function:
1\. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation ≥ 30 ml/min/1.73 m\^2.
3. Hepatic function:
1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) (or \< 5 x ULN for participants with liver involvement).
2. total bilirubin (TBL) \< 1.5 x ULN (or \< 2 x ULN for participants with liver metastases).
4. Cardiac function:
1. 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).
2. Baseline electrocardiogram (ECG) QTcF ≤ 470 msec (average of triplicate values).
5. Pulmonary function:
1. baseline oxygen saturation \> 92% on room air at rest and no oxygen supplementation.
Part 3-Retreatment group:
* Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following:
1. confirmed PSA50 response.
2. radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with AMG 509 and without progression during the first 6 cycles.
* No discontinuation for toxicity during the initial treatment with 6 cycles of AMG 509.
* Progressive disease as defined in I106 within 12 months of final dose in their initial treatment with 6 cycles (EOT\_1).
* Willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator.
Exclusion Criteria
* 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. 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. 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 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 prostate specific membrane antigen (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 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.
18 Years
MALE
No
Sponsors
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BeiGene
INDUSTRY
BeOne (China only)
UNKNOWN
Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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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
MidAmerica Cancer Care
Merriam, Kansas, United States
Tulane Medical Center
New Orleans, Louisiana, United States
Washington University
St 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
United States Oncology Regulatory Affairs Corporate Office
Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
US Oncology Research Investigational Products Center
Irving, 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
Peking University First Hospital
Beijing, Beijing Municipality, China
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 Municipality, China
Zhejiang Provincial Peoples Hospital
Hangzhou, Zhejiang, China
Universitaetsklinikum Essen
Essen, , Germany
Universitaetsklinikum Heidelberg
Heidelberg, , Germany
Klinikum rechts der Isar der TUM
München, , Germany
Universitaetsklinikum Muenster
Münster, , Germany
National Cancer Center Hospital East
Kashiwa-shi, Chiba, Japan
Yokohama City University Hospital
Yokohama, Kanagawa, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, Japan
Hospital da Luz, SA
Lisbon, , Portugal
Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
Lisbon, , Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
Porto, , Portugal
Seoul National University Hospital
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, 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
Kantonsspital Sankt Gallen
Sankt Gallen, , Switzerland
National Taiwan University Hospital
Taipei, , Taiwan
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Taoyuan District, , Taiwan
Countries
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Central Contacts
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References
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Kelly WK, Danila DC, Lin CC, Lee JL, Matsubara N, Ward PJ, Armstrong AJ, Pook D, Kim M, Dorff TB, Fischer S, Lin YC, Horvath LG, Sumey C, Yang Z, Jurida G, Smith KM, Connarn JN, Penny HL, Stieglmaier J, Appleman LJ. Xaluritamig, a STEAP1 x CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study. Cancer Discov. 2024 Jan 12;14(1):76-89. doi: 10.1158/2159-8290.CD-23-0964.
Kuipers-Connarn JN, Pourzanjani A, Bose M, Modi S, Stieglmaier J, Murphy A, Mehta K, Upreti VV. Clinical Pharmacology Characterization and Dose Selection of Xaluritamig, a Next Generation XmAb(R) 2+1 T-Cell Engager, in Prostate Cancer Patients. J Clin Pharmacol. 2025 Dec;65(12):1676-1686. doi: 10.1002/jcph.70074. Epub 2025 Aug 5.
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2023-504361-23
Identifier Type: OTHER
Identifier Source: secondary_id
20180146
Identifier Type: -
Identifier Source: org_study_id
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