Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer

NCT04221542 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 201801462023-504361-23
• Study Type: interventional
• Target: 479
• Locations: 10 countries
• Sites: 57

Brief Summary

The overall aim of the trial is to evaluate the safety, tolerability, and pharmacokinetics (PK) of AMG 509 (monotherapy and in combination with abiraterone acetate and enzalutamide) and to evaluate preliminary efficacy. As of Protocol Amendment 10 (09 July 2025), only Parts 4A expansion, 6, and 7 are open to accrual.

Conditions

Prostate Cancer

Keywords

AMG 509; mCRPC; Metastatic Castration-resistant Prostate Cancer; Prostate cancer; PSMA; STEAP1; STEAP1 targeted therapy; Solid tumor; Immunotherapy; Immuno-oncology; Immunooncology; Bispecific T-Cell engager®; BiTE®; XmAb®

Outcome Measures

Primary Outcomes (7)

• Parts 1-5 and 7: Incidence of Treatment-emergent Adverse Events

  3 years

• Parts 1-5 and 7: Incidence of Treatment-related Adverse Events

  3 years

• Parts 1-5 and 7 Dose Exploration Cohorts Only: Dose Limiting Toxicities (DLTs)

  28 days

• Parts 1-5 and 7: Number of Participants with Changes in Vital Signs

  3 years

• Parts 1-5 and 7: Number of Participants with Changes in Electrocardiogram (ECG) Records

  3 years

• Parts 1-5 and 7: Number of Participants with Changes in Clinical Laboratory Test Results

  3 years

• Part 6: Objective Response (OR) per RECIST v1.1

  3 years

Secondary Outcomes (32)

• Parts 1-7: Maximum Serum Concentration (Cmax) for AMG 509

  3 years

• Parts 1-7: Time to Maximum Serum Concentration (Tmax) for AMG 509

  3 years

• Parts 1-7: Minimum Serum Concentration (Cmin) for AMG 509

  3 years

• Parts 1-7: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval for AMG 509

  3 years

• Parts 1-7: Accumulation Following Multiple Dosing for AMG 509

  3 years

Study Arms (7)

Part 1: AMG 509 Intravenous (IV) Monotherapy

EXPERIMENTAL

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.

Drug: AMG 509

Part 2: AMG 509 Subcutaneous (SC) Monotherapy

EXPERIMENTAL

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.

Drug: AMG 509

Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment

EXPERIMENTAL

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.

Drug: AMG 509

Part 4: AMG 509 IV Combination Therapy

EXPERIMENTAL

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.

Drug: AMG 509; Drug: Abiraterone; Drug: Enzalutamide

Part 5: AMG 509 IV Monotherapy in Outpatient Setting

EXPERIMENTAL

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.

Drug: AMG 509

Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate

EXPERIMENTAL

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.

Drug: AMG 509; Drug: Abiraterone

Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate

EXPERIMENTAL

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.

Drug: AMG 509; Drug: Abiraterone

Interventions

AMG 509 DRUG

AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).

Also known as: xaluritamig

Part 1: AMG 509 Intravenous (IV) Monotherapy; Part 2: AMG 509 Subcutaneous (SC) Monotherapy; Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment; Part 4: AMG 509 IV Combination Therapy; Part 5: AMG 509 IV Monotherapy in Outpatient Setting; Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate; Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate

Abiraterone DRUG

Abiraterone administered as oral tablets.

Part 4: AMG 509 IV Combination Therapy; Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate; Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate

Enzalutamide DRUG

Enzalutamide administered as oral tablets.

Part 4: AMG 509 IV Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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:
• 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.
• A: 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:
• 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.
• No prior treatment with any chemotherapy regimen in the mCRPC setting; ≤ 6 cycles of docetaxel treatment in the mHSPC setting is allowed.
• mCRPC with ≥ 1 RECIST v1.1 measurable lesion that is present on baseline computed tomography (CT) or magnetic resonance imaging (MRI).
• All parts:

You may not qualify if:

• 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. 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.

Sponsors & Collaborators

• Amgen: lead
• BeiGene: collaborator
• BeOne (China only): collaborator

Study Sites (57)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Providence Saint Jude Medical Center

Fullerton, California, 92835, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

MidAmerica Cancer Care

Merriam, Kansas, 66204, United States

RECRUITING

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

COMPLETED

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Oncology Hematology Care Incorporated

Cincinnati, Ohio, 45242, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Prisma Health Upstate

Greenville, South Carolina, 29605, United States

COMPLETED

Sanford Oncology Clinic and Pharmacy

Sioux Falls, South Dakota, 57104, United States

RECRUITING

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

US Oncology Research Investigational Products Center

Irving, Texas, 75063, United States

RECRUITING

Intermountain Medical Center

Murray, Utah, 84107, United States

RECRUITING

Virginia Cancer Specialists PC

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

Fudan University Shanghai Cancer Centre

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Zhejiang Provincial Peoples Hospital

Hangzhou, Zhejiang, 314408, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, 210003, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000, China

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Klinikum rechts der Isar der TUM

München, 81675, Germany

RECRUITING

Universitaetsklinikum Muenster

Münster, 48149, Germany

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

RECRUITING

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

Hospital da Luz, SA

Lisbon, 1500-650, Portugal

RECRUITING

Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

RECRUITING

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 138-736, South Korea

RECRUITING

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

RECRUITING

Kantonsspital Graubuenden

Chur, 7000, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

RECRUITING

Kantonsspital Sankt Gallen

Sankt Gallen, 9007, Switzerland

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

RECRUITING

Related Publications (2)

• 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.

  PMID: 37861461 BACKGROUND

• 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.

  PMID: 40765197 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Prostatic Neoplasms; Bites and Stings

Interventions

abiraterone; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: January 9, 2020
• Study Start: March 4, 2020
• Primary Completion (Estimated): March 22, 2030
• Study Completion (Estimated): March 21, 2032
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (25); TW (2); ES (5); PT (3); DE (4); CN (7); AU (2); CH (4); JP (3); KR (2)