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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04221542




Registration number
NCT04221542
Ethics application status
Date submitted
16/12/2019
Date registered
9/01/2020
Date last updated
22/09/2020

Titles & IDs
Public title
Study of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Scientific title
A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Secondary ID [1] 0 0
20180146
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 509
Treatment: Drugs - Dexamethasone

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.

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.


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

Treatment: Drugs: Dexamethasone
Dexamethasone (or equivalent corticosteroids) will be administered prior to dosing during cycle 1

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events
Timepoint [1] 0 0
3 years
Primary outcome [2] 0 0
Incidence of treatment-related adverse events
Timepoint [2] 0 0
3 years
Primary outcome [3] 0 0
Dose limiting toxicities (DLTs)
Timepoint [3] 0 0
3 years
Primary outcome [4] 0 0
Number of participants with changes in vital signs
Timepoint [4] 0 0
3 years
Primary outcome [5] 0 0
Number of participants with changes in the electrocardiogram (ECG) records.
Timepoint [5] 0 0
3 years
Primary outcome [6] 0 0
Number of participants with changes in the clinical laboratory tests results.
Timepoint [6] 0 0
3 years
Secondary outcome [1] 0 0
Maximum serum concentration (Cmax) for AMG 509 - To characterize the pharmacokinetics (PK) of AMG 509
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Minimum serum concentration (Cmin) for AMG 509 - To characterize the pharmacokinetics (PK) of AMG 509
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Area under the concentration-time curve (AUC) over the dosing interval for AMG 509 - To characterize the pharmacokinetics (PK) of AMG 509
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Accumulation following multiple dosing for AMG 509 - To characterize the pharmacokinetics (PK) of AMG 509
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Prostate specific antigen (PSA) response - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
Duration of response (DOR) (radiographic and PSA) - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Time to progression (radiographic and PSA) - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
Progression-free survival (PFS) (radiographic and PSA) - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [9] 0 0
3 years
Secondary outcome [10] 0 0
1, 2, and 3-year overall survival (OS) - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [10] 0 0
Year 1, 2, and 3
Secondary outcome [11] 0 0
Circulating tumor cells response (CTC0) - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
Rate of circulating tumor cells CTC conversion - To evaluate preliminary anti-tumor activity of AMG 509
Timepoint [12] 0 0
3 years
Secondary outcome [13] 0 0
time to symptomatic skeletal events. - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [13] 0 0
3 years
Secondary outcome [14] 0 0
alkaline phosphatase (total, bone) - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [14] 0 0
3 years
Secondary outcome [15] 0 0
lactate dehydrogenase (LDH) - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [15] 0 0
3 years
Secondary outcome [16] 0 0
hemoglobin - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [16] 0 0
3 years
Secondary outcome [17] 0 0
urine N-telopeptide - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [17] 0 0
3 years
Secondary outcome [18] 0 0
neutrophil-to-lymphocyte ratio - To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.
Timepoint [18] 0 0
3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Clayton
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
Japan
State/province [5] 0 0
Kashiwa-shi

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT04221542
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04221542