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Trial details imported from ClinicalTrials.gov

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




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

Titles & IDs
Public title
Study of AMG 509 in Participants 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
2021-005052-11
Secondary ID [2] 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 - Abiraterone
Treatment: Drugs - Enzalutamide

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.

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.

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.

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 0/2 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.

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


Treatment: Drugs: AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).

Treatment: Drugs: Abiraterone
Abiraterone administered as oral tablets.

Treatment: Drugs: Enzalutamide
Enzalutamide administered as oral tablets.
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
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Time to maximum serum concentration (Tmax) for AMG 509
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Minimum serum concentration (Cmin) for AMG 509
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Area under the concentration-time curve (AUC) over the dosing interval for AMG 509
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Accumulation following multiple dosing for AMG 509
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
Prostate specific antigen (PSA) response
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
PSA decline of at least 50% from baseline at 12 weeks
Timepoint [8] 0 0
Week 12
Secondary outcome [9] 0 0
Duration of response (DOR) (radiographic and PSA)
Timepoint [9] 0 0
3 years
Secondary outcome [10] 0 0
Time to progression (radiographic and PSA)
Timepoint [10] 0 0
3 years
Secondary outcome [11] 0 0
Progression-free survival (PFS) (radiographic and PSA)
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
6 month radiographic PFS
Timepoint [12] 0 0
6 months
Secondary outcome [13] 0 0
1, 2, and 3-year radiographic PFS
Timepoint [13] 0 0
Year 1, 2, and 3
Secondary outcome [14] 0 0
1, 2, and 3-year overall survival (OS)
Timepoint [14] 0 0
Year 1, 2, and 3
Secondary outcome [15] 0 0
Circulating tumor cells response (CTC0)
Timepoint [15] 0 0
3 years
Secondary outcome [16] 0 0
Rate of circulating tumor cells (CTC) conversion
Timepoint [16] 0 0
3 years
Secondary outcome [17] 0 0
Time to symptomatic skeletal events
Timepoint [17] 0 0
3 years
Secondary outcome [18] 0 0
Alkaline phosphatase (total, bone)
Timepoint [18] 0 0
3 years
Secondary outcome [19] 0 0
Lactate dehydrogenase (LDH)
Timepoint [19] 0 0
3 years
Secondary outcome [20] 0 0
Hemoglobin
Timepoint [20] 0 0
3 years
Secondary outcome [21] 0 0
Urine N-telopeptide
Timepoint [21] 0 0
3 years
Secondary outcome [22] 0 0
Neutrophil-to-lymphocyte ratio
Timepoint [22] 0 0
3 years

Eligibility
Key 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 (no prior taxanes). 0-1 prior PARP inhibitors or sipuleucel-T treatments are acceptable. Participants who received prior investigational therapy for the treatment of metastatic disease are not eligible.
* Parts 4A and 4B:

1. Participants with histologically or cytologically confirmed mCRPC who are refractory to 0-2 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).

Part 3-Retreatment group:

* Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following:

1. confirmed PSA50 response.
2. radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with AMG 509 and without progression during the first 6 cycles.
* No discontinuation for toxicity during the initial treatment with 6 cycles of AMG 509.
* Progressive disease as defined in I106 within 12 months of final dose in their initial treatment with 6 cycles (EOT_1).
* Willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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).
* 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. Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible (exception: part 3 retreatment).
* Part 3-Retreatment only: Any anticancer therapy or immunotherapy, not including luteinizing hormone-releasing hormone/gonadotropin releasing hormone (LHRH/GnRH) analogue (agonist/antagonist), and/or bisphosphonate or denosumab regimen after last dose of AMG 509 initial course of treatment.

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
4/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/07/2028
Actual
Sample size
Target
461
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Monash Medical Centre - 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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
South Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
China
State/province [19] 0 0
Guangdong
Country [20] 0 0
China
State/province [20] 0 0
Jiangxi
Country [21] 0 0
China
State/province [21] 0 0
Shanghai
Country [22] 0 0
China
State/province [22] 0 0
Zhejiang
Country [23] 0 0
Germany
State/province [23] 0 0
Essen
Country [24] 0 0
Germany
State/province [24] 0 0
Heidelberg
Country [25] 0 0
Germany
State/province [25] 0 0
Muenchen
Country [26] 0 0
Germany
State/province [26] 0 0
Muenster
Country [27] 0 0
Japan
State/province [27] 0 0
Chiba
Country [28] 0 0
Japan
State/province [28] 0 0
Kanagawa
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Portugal
State/province [31] 0 0
Lisboa
Country [32] 0 0
Portugal
State/province [32] 0 0
Porto
Country [33] 0 0
Spain
State/province [33] 0 0
Cataluña
Country [34] 0 0
Spain
State/province [34] 0 0
Navarra
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Switzerland
State/province [36] 0 0
Bellinzona
Country [37] 0 0
Switzerland
State/province [37] 0 0
Chur
Country [38] 0 0
Switzerland
State/province [38] 0 0
Lausanne
Country [39] 0 0
Switzerland
State/province [39] 0 0
Sankt Gallen
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taipei
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taoyuan

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04221542