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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04221542
Recruitment Status : Recruiting
First Posted : January 9, 2020
Last Update Posted : April 12, 2024
Sponsor:
Information provided by (Responsible Party):
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).

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

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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 8, 2026
Estimated Study Completion Date : July 30, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04221542


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

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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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    Key Record Dates
Last Update Posted: April 12, 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

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