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

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer

Evaluate the safety and tolerability of AMG 509 in adult participants and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: AMG 509; Drug: Abiraterone; Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Estimated): 461
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris OBrien Lifehouse
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University, Cancer Center
  • Zhejiang
    • Hangzhou, Zhejiang, China, 314408
      • Recruiting
      • Zhejiang Provincial Peoples Hospital
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
  • Muenchen, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar der TUM
  • Muenster, Germany, 48149
    • Recruiting
    • Universitaetsklinikum Muenster
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 236-0004
      • Recruiting
      • Yokohama City University Hospital
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 138-736
    • Recruiting
    • Asan Medical Center
• Portugal
  • Lisboa, Portugal, 1500-650
    • Recruiting
    • Hospital da Luz, SA
  • Porto, Portugal, 4200-072
    • Recruiting
    • Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
    • Barcelona, Cataluña, Spain, 08036
      • Recruiting
      • Hospital Clinic i Provincial de Barcelona
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Recruiting
    • Istituto Oncologico della Svizzera Italiana
  • Chur, Switzerland, 7000
    • Recruiting
    • Kantonsspital Graubuenden
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois
  • Sankt Gallen, Switzerland, 9007
    • Recruiting
    • Kantonsspital Sankt Gallen
• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
    • Fullerton, California, United States, 92835
      • Recruiting
      • Providence Saint Jude Medical Center
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Cancer Center
  • Kansas
    • Merriam, Kansas, United States, 66204
      • Recruiting
      • Alliance for Multispecialty Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Completed
      • Tulane Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Oncology Hematology Care Incorporated
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center Cancer Pavillion
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Completed
      • Prisma Health Upstate
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Health
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

  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 are refractory to a NHT (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.

• Parts 4A and 4B:

  1. Participants with histologically or cytologically confirmed mCRPC who have received no or 1/2 prior NHT (given in any disease setting depending on the part), and no or 1 taxane (given for hormone sensitive prostate cancer).
  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.
  4. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
• 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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications.
  3. appearance of 2 or more new lesions in bone scan.
• Eastern Cooperative Oncology Group performance status of 0-1.

• 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).

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.
• 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). Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 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.	Drug: AMG 509; AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).; Other Names: xaluritamig
Experimental: 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.	Drug: AMG 509; AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).; Other Names: xaluritamig
Experimental: Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment; Part 3 will explore AMG 509 in participants with mCRPC who have received 1 prior NHT (may have been given for HSPC) and no prior taxanes (may have been given for HSPC). 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; AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).; Other Names: xaluritamig
Experimental: 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 1/2 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.	Drug: AMG 509; AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).; Other Names: xaluritamig; Drug: Abiraterone; Abiraterone administered as oral tablets.; Drug: Enzalutamide; Enzalutamide administered as oral tablets.
Experimental: 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 DLRT recommendations and will utilize the doses explored in Part 1 dose-expansion phase	Drug: AMG 509; AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).; Other Names: xaluritamig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events	3 years
Incidence of treatment-related 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration (Cmax) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Time to maximum serum concentration (Tmax) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Minimum serum concentration (Cmin) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Area under the concentration-time curve (AUC) over the dosing interval for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Accumulation following multiple dosing for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Prostate specific antigen (PSA) response	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Duration of response (DOR) (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Time to progression (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Progression-free survival (PFS) (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
1, 2, and 3-year overall survival (OS)	To evaluate preliminary anti-tumor activity of AMG 509	Year 1, 2, and 3
Circulating tumor cells response (CTC0)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Time to symptomatic skeletal events	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Alkaline phosphatase (total, bone)	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Lactate dehydrogenase (LDH)	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Hemoglobin	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Urine N-telopeptide	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Neutrophil-to-lymphocyte ratio	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
PSA decline of at least 50% from baseline at 12 weeks	To evaluate preliminary anti-tumor activity of AMG 509	Week 12
6 month radiographic PFS	To evaluate preliminary anti-tumor activity of AMG 509	6 months
1, 2, and 3-year radiographic PFS	To evaluate preliminary anti-tumor activity of AMG 509	Year 1, 2, and 3
Rate of circulating tumor cells (CTC) conversion	To evaluate preliminary anti-tumor activity of AMG 509	3 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Estimated): April 8, 2026
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Prostate cancer; Solid tumor; mCRPC; PSMA; Immuno-oncology; Immunooncology; Metastatic Castration-resistant Prostate Cancer; BiTE®; AMG 509; STEAP1; STEAP1 targeted therapy; Bispecific T-Cell engager®; XmAb®
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 20180146 (Ethics comitee); 2021-005052-11 (EudraCT Number); 2023-504361-23 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No