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

• ClinicalTrials.gov Identifier: NCT04221542
• Recruitment Status: Recruiting
• First Posted: January 9, 2020
• Last Update Posted: April 25, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: AMG 509; Drug: Abiraterone; Drug: Enzalutamide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 461 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer
• Actual Study Start Date: March 4, 2020
• Estimated Primary Completion Date: April 15, 2026
• Estimated Study Completion Date: July 30, 2028

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: xaluritamig

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events [ Time Frame: 3 years ]
2. Incidence of treatment-related adverse events [ Time Frame: 3 years ]
3. Dose limiting toxicities (DLTs) [ Time Frame: 3 years ]
4. Number of participants with changes in vital signs [ Time Frame: 3 years ]
5. Number of participants with changes in the electrocardiogram (ECG) records [ Time Frame: 3 years ]
6. Number of participants with changes in the clinical laboratory tests results [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. Maximum serum concentration (Cmax) for AMG 509 [ Time Frame: 3 years ]
   To characterize the pharmacokinetics (PK) of AMG 509
2. Time to maximum serum concentration (Tmax) for AMG 509 [ Time Frame: 3 years ]
   To characterize the pharmacokinetics (PK) of AMG 509
3. Minimum serum concentration (Cmin) for AMG 509 [ Time Frame: 3 years ]
   To characterize the pharmacokinetics (PK) of AMG 509
4. Area under the concentration-time curve (AUC) over the dosing interval for AMG 509 [ Time Frame: 3 years ]
   To characterize the pharmacokinetics (PK) of AMG 509
5. Accumulation following multiple dosing for AMG 509 [ Time Frame: 3 years ]
   To characterize the pharmacokinetics (PK) of AMG 509
6. Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications [ Time Frame: 3 years ]
   To evaluate preliminary anti-tumor activity of AMG 509
7. Prostate specific antigen (PSA) response [ Time Frame: 3 years ]
   To evaluate preliminary anti-tumor activity of AMG 509
8. PSA decline of at least 50% from baseline at 12 weeks [ Time Frame: Week 12 ]
   To evaluate preliminary anti-tumor activity of AMG 509
9. Duration of response (DOR) (radiographic and PSA) [ Time Frame: 3 years ]
   To evaluate preliminary anti-tumor activity of AMG 509
10. Time to progression (radiographic and PSA) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509
11. Progression-free survival (PFS) (radiographic and PSA) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509
12. 6 month radiographic PFS [ Time Frame: 6 months ]
    To evaluate preliminary anti-tumor activity of AMG 509
13. 1, 2, and 3-year radiographic PFS [ Time Frame: Year 1, 2, and 3 ]
    To evaluate preliminary anti-tumor activity of AMG 509
14. 1, 2, and 3-year overall survival (OS) [ Time Frame: Year 1, 2, and 3 ]
    To evaluate preliminary anti-tumor activity of AMG 509
15. Circulating tumor cells response (CTC0) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509
16. Rate of circulating tumor cells (CTC) conversion [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509
17. Time to symptomatic skeletal events [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
18. Alkaline phosphatase (total, bone) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
19. Lactate dehydrogenase (LDH) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
20. Hemoglobin [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
21. Urine N-telopeptide [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
22. Neutrophil-to-lymphocyte ratio [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

Locations

United States, California

City of Hope National Medical Center; Recruiting

Duarte, California, United States, 91010

Providence Saint Jude Medical Center; Recruiting

Fullerton, California, United States, 92835

University of California San Francisco; Recruiting

San Francisco, California, United States, 94158

United States, Connecticut

Yale Cancer Center; Recruiting

New Haven, Connecticut, United States, 06520

United States, Georgia

Emory University; Recruiting

Atlanta, Georgia, United States, 30322

United States, Indiana

Indiana University Melvin and Bren Simon Cancer Center; Recruiting

Indianapolis, Indiana, United States, 46202

United States, Kansas

Alliance for Multispecialty Research; Recruiting

Merriam, Kansas, United States, 66204

United States, Louisiana

Tulane Medical Center; Completed

New Orleans, Louisiana, United States, 70112

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

United States, Ohio

Oncology Hematology Care Incorporated; Recruiting

Cincinnati, Ohio, United States, 45242

United States, Pennsylvania

Thomas Jefferson University; Recruiting

Philadelphia, Pennsylvania, United States, 19107

University of Pittsburgh Medical Center Cancer Pavillion; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Prisma Health Upstate; Completed

Greenville, South Carolina, United States, 29605

United States, South Dakota

Sanford Health; Recruiting

Sioux Falls, South Dakota, United States, 57104

United States, Texas

University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

United States, Washington

Fred Hutchinson Cancer Center; Recruiting

Seattle, Washington, United States, 98109

Australia, New South Wales

Chris OBrien Lifehouse; Recruiting

Camperdown, New South Wales, Australia, 2050

Australia, Victoria

Monash Medical Centre; Recruiting

Clayton, Victoria, Australia, 3168

China, Guangdong

Sun Yat-sen University, Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510060

China, Shanghai

Fudan University Shanghai Cancer Centre; Recruiting

Shanghai, Shanghai, China, 200032

China, Zhejiang

Zhejiang Provincial Peoples Hospital; Recruiting

Hangzhou, Zhejiang, China, 314408

Germany

Universitaetsklinikum Essen; Recruiting

Essen, Germany, 45147

Universitaetsklinikum Heidelberg; Recruiting

Heidelberg, Germany, 69120

Klinikum rechts der Isar der TUM; Recruiting

Muenchen, Germany, 81675

Universitaetsklinikum Muenster; Recruiting

Muenster, Germany, 48149

Japan

National Cancer Center Hospital East; Recruiting

Kashiwa-shi, Chiba, Japan, 277-8577

Yokohama City University Hospital; Recruiting

Yokohama-shi, Kanagawa, Japan, 236-0004

The Cancer Institute Hospital of Japanese Foundation for Cancer Research; Recruiting

Koto-ku, Tokyo, Japan, 135-8550

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 138-736

Portugal

Hospital da Luz, SA; Recruiting

Lisboa, Portugal, 1500-650

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE; Recruiting

Porto, Portugal, 4200-072

Spain

Hospital Universitari Vall d Hebron; Recruiting

Barcelona, Cataluña, Spain, 08035

Hospital Clinic i Provincial de Barcelona; Recruiting

Barcelona, Cataluña, Spain, 08036

Clinica Universidad de Navarra; Recruiting

Pamplona, Navarra, Spain, 31008

Hospital Clinico San Carlos; Recruiting

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre; Recruiting

Madrid, Spain, 28041

Switzerland

Istituto Oncologico della Svizzera Italiana; Recruiting

Bellinzona, Switzerland, 6500

Kantonsspital Graubuenden; Recruiting

Chur, Switzerland, 7000

Centre Hospitalier Universitaire Vaudois; Recruiting

Lausanne, Switzerland, 1011

Kantonsspital Sankt Gallen; Recruiting

Sankt Gallen, Switzerland, 9007

Taiwan

National Taiwan University Hospital; Recruiting

Taipei, Taiwan, 10002

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation; Recruiting

Taoyuan, Taiwan, 33305

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT04221542
• Other Study ID Numbers: 20180146; 2021-005052-11 ( EudraCT Number ); 2023-504361-23 ( Other Identifier: EU CT Number )
• First Posted: January 9, 2020
• Last Update Posted: April 25, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.
• URL: http://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

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®

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases