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

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ClinicalTrials.gov Identifier: NCT04221542
Recruitment Status : Recruiting
First Posted : January 9, 2020
Last Update Posted : January 20, 2021
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 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 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 : October 22, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Dose exploration phase

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).

Recommended phase 2 dose (RP2D) may be identified based on emerging safety, efficacy, PK, and PD data prior to reaching an MTD. Alternative dosing schedule(s) (including a second step dose) may be explored based on emerging safety and PK data.

Drug: AMG 509
AMG 509 administered as a short-term IV infusion in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Experimental: Dose expansion phase
A dose expansion phase will be conducted to 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 a short-term IV infusion in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC).




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. Minimum serum concentration (Cmin) for AMG 509 [ Time Frame: 3 years ]
    To characterize the pharmacokinetics (PK) of AMG 509

  3. 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

  4. Accumulation following multiple dosing for AMG 509 [ Time Frame: 3 years ]
    To characterize the pharmacokinetics (PK) of AMG 509

  5. 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

  6. Prostate specific antigen (PSA) response [ Time Frame: 3 years ]
    To evaluate preliminary anti-tumor activity of AMG 509

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

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

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

  10. 1, 2, and 3-year overall survival (OS) [ Time Frame: Year 1, 2, and 3 ]
    To evaluate preliminary anti-tumor activity of AMG 509

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

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

  13. 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.

  14. 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.

  15. 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.

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

  17. 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.

  18. 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

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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:

  • Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
  • Age is greater than or equal to 18 years
  • Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone and/or enzalutamide)) 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).
  • Dose escalation: novel antiandrogen therapy must have been given for treatment of metastatic disease
  • Dose expansion: progression on novel antiandrogen therapy may have occurred in the non-metastatic or metastatic setting
  • Subjects must have undergone bilateral orchiectomy or be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist
  • Total serum testosterone is less than or equal to 50 ng/dL or 1.7 nmol/L
  • Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
  • PSA level is greater than or equal to 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
  • nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
  • appearance of 2 or more new lesions in bone scan
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Life expectancy greater than or equal to 3 months
  • Adequate organ function, defined as follows:

Hematological function:

  • absolute neutrophil count is greater than or equal to 1 x 109/L (without growth factor support within 7 days from screening assessment)
  • platelet count is greater than or equal to 75 x 109/L (without platelet transfusion within 7 days from screening assessment)
  • hemoglobin is greater than or equal to 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment)

Renal function:

  • estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation is greater than or equal to 30 ml/min/1.73 m2

Hepatic function:

  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is less than 3 x ULN (or less than 5 x ULN for subjects with liver involvement)
  • total bilirubin (TBL) is less than 1.5 x ULN (or is less than 2 x ULN for subjects with liver metastases)

Cardiac function:

  • left ventricular ejection fraction is greater than 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi gated acquisition scan is acceptable if ECHO is not available)
  • baseline ECG QTcF is less than 470 msec

Exclusion Criteria:

Disease Related

  • 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. Patients 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.

Other Medical Conditions

  • Prior major surgery within 4 weeks of first dose
  • Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
  • Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management within 7 days of dosing NOTE: 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
  • Positive test for human immunodeficiency virus (HIV)
  • Exclusion of hepatitis infection based on the following results and/or criteria:
  • Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).
  • Negative HBsAg and positive for hepatitis B core antibody: Hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
  • Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
  • History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis) within 12 months of first dose of AMG 509
  • Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509
  • Unresolved toxicities from prior anti-tumor therapy not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, with the exception of alopecia or toxicities that are stable and well-controlled AND there is agreement to allow by both the investigator and sponsor
  • History of other malignancy within the past 2 years, with the following exception(s):
  • malignancy treated with curative intent and with no known active disease present for greater than or equal to 1 years before enrollment and felt to be at low risk for recurrence by the treating physician
  • adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
  • History or evidence of inflammatory bowel disease (ulcerative colitis or Crohn disease) or any other gastrointestinal disorder causing chronic nausea, vomiting, or diarrhea (defined as greater than or equal to 2 CTCAE grade 2)
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis, or uncontrolled asthma Prior/Concomitant Therapy
  • Prior STEAP1-targeted therapy
  • Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including LHRH/GnRH analogue (agonist/antagonist). Subjects on a stable bisphosphonate or denosumab regimen for greater or equal than 30 days prior to enrollment are eligible.
  • Requirement for chronic systemic corticosteroid therapy (prednisone dose greater than 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti TNF-alpha therapies) unless stopped (with adequate tapering) within 7 days prior to dosing Prior/Concurrent Clinical Study Experience
  • Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Other Exclusions

  • Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 6 months after the last dose of AMG 509. Refer to Section 12.5 for additional contraceptive information.
  • Subject has known sensitivity to any components of AMG 509 to be administered during dosing.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

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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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
United States, Louisiana
Research Site Recruiting
New Orleans, Louisiana, United States, 70112
United States, New York
Research Site Recruiting
New York, New York, United States, 10065
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45242
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19107
Research Site Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Research Site Recruiting
Greenville, South Carolina, United States, 29605
United States, South Dakota
Research Site Recruiting
Sioux Falls, South Dakota, United States, 57104
Australia, New South Wales
Research Site Recruiting
Camperdown, New South Wales, Australia, 2050
Australia
Research Site Recruiting
Clayton, Australia, 3168
Japan
Research Site Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
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: January 20, 2021
Last Verified: January 2021
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