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Study of AMG 509 in Subjects 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 : March 18, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Evaluate the safety and tolerability of AMG 509 in adult subjects 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 : 359 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 : October 22, 2025
Estimated Study Completion Date : May 7, 2027

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 and 4) or SC injection (Part 2).

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.

The dose exploration phase of Part 2 of the study will estimate the MTD of AMG 509 SC using a BLRM (Neuenschwander et al, 2008).

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 and 4) or SC injection (Part 2).

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. 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 and 4) or SC injection (Part 2).

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 1 prior NHT, at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A) or enzalutamide (Part 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.

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

Drug: Abiraterone
Abiraterone administered as oral tablets.

Drug: Enzalutamide
Enzalutamide administered as oral tablets.




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. Duration of response (DOR) (radiographic and PSA) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

  9. Time to progression (radiographic and PSA) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

  10. Progression-free survival (PFS) (radiographic and PSA) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

  11. 1, 2, and 3-year overall survival (OS) [ Time Frame: Year 1, 2, and 3 ]
    To evaluate preliminary anti-tumor activity of AMG 509

  12. Circulating tumor cells response (CTC0) [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

  13. Rate of circulating tumor cells CTC conversion [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

  14. 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.

  15. 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.

  16. 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.

  17. Hemoglobin [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.

  18. 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.

  19. 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: Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone and/or enzalutamide, apalutamide, darolutamide, bicalutamide, or equivalent) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen).

    1. Dose exploration phase: novel antiandrogen therapy must have been given for treatment of metastatic disease.
    2. Dose expansion phase: progression on novel antiandrogen therapy may have occurred in the non-metastatic or metastatic setting.
  • Parts 4A and 4B:

    1. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) given for hormone-sensitive prostate cancer (HSPC) or non-metastatic CRPC and have failed up to 1 taxane regimen for HSPC (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen).
    2. 4A: Participants planning to receive abiraterone for the first time (participants who received prior abiraterone are not eligible).
    3. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
  • Parts 3

    a. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) 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.

  • Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy (ADT) 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 (ECOG) 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 MDRD (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.

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.
  • 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.
  • Any anticancer 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.

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
First Posted: January 9, 2020    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022
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
Prostatic Diseases