Clinical Trials /

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

NCT04221542

Description:

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

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 20180146
  • NCT ID: NCT04221542

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
AMG 509Dose expansion phase
DexamethasoneDose expansion phase

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Dose exploration phaseExperimentalThe 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.
  • AMG 509
  • Dexamethasone
Dose expansion phaseExperimentalA 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.
  • AMG 509
  • Dexamethasone

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events
Time Frame:3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum serum concentration (Cmax) for AMG 509
Time Frame:3 years
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of AMG 509
Measure:Minimum serum concentration (Cmin) for AMG 509
Time Frame:3 years
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of AMG 509
Measure:Area under the concentration-time curve (AUC) over the dosing interval for AMG 509
Time Frame:3 years
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of AMG 509
Measure:Accumulation following multiple dosing for AMG 509
Time Frame:3 years
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of AMG 509
Measure: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
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Prostate specific antigen (PSA) response
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Duration of response (DOR) (radiographic and PSA)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Time to progression (radiographic and PSA)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Progression-free survival (PFS) (radiographic and PSA)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:1, 2, and 3-year overall survival (OS)
Time Frame:Year 1, 2, and 3
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Circulating tumor cells response (CTC0)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:Rate of circulating tumor cells CTC conversion
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509
Measure:time to symptomatic skeletal events.
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Measure:alkaline phosphatase (total, bone)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Measure:lactate dehydrogenase (LDH)
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Measure:hemoglobin
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Measure:urine N-telopeptide
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Measure:neutrophil-to-lymphocyte ratio
Time Frame:3 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • 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®

Last Updated

February 6, 2020