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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04221542

Studienbeginn:
März 2020

Letztes Update:
25.04.2024

Wirkstoff:
AMG 509, Abiraterone, Enzalutamide

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Amgen

Collaborator:
-

Studienleiter

MD
Study Director
Amgen

Kontakt

Studienlocations
(3 von 45)

Universitaetsklinikum Essen
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Klinikum rechts der Isar der TUM
81675 Muenchen
(Bayern)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Muenster
48149 Muenster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
City of Hope National Medical Center
91010 Duarte
United StatesRekrutierend» Google-Maps
Providence Saint Jude Medical Center
92835 Fullerton
United StatesRekrutierend» Google-Maps
University of California San Francisco
94158 San Francisco
United StatesRekrutierend» Google-Maps
Indiana University Melvin and Bren Simon Cancer Center
46202 Indianapolis
United StatesRekrutierend» Google-Maps
Alliance for Multispecialty Research
66204 Merriam
United StatesRekrutierend» Google-Maps
Tulane Medical Center
70112 New Orleans
United StatesAbgeschlossen» Google-Maps
Washington University
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
Duke University Medical Center
27710 Durham
United StatesRekrutierend» Google-Maps
Oncology Hematology Care Incorporated
45242 Cincinnati
United StatesRekrutierend» Google-Maps
Thomas Jefferson University
19107 Philadelphia
United StatesRekrutierend» Google-Maps
University of Pittsburgh Medical Center Cancer Pavillion
15232 Pittsburgh
United StatesRekrutierend» Google-Maps
Prisma Health Upstate
29605 Greenville
United StatesAbgeschlossen» Google-Maps
University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Fred Hutchinson Cancer Center
98109 Seattle
United StatesRekrutierend» Google-Maps
Sun Yat-sen University, Cancer Center
510060 Guangzhou
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Fudan University Shanghai Cancer Centre
200032 Shanghai
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Zhejiang Provincial Peoples Hospital
314408 Hangzhou
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National Cancer Center Hospital East
277-8577 Kashiwa-shi
JapanRekrutierend» Google-Maps
Yokohama City University Hospital
236-0004 Yokohama-shi
JapanRekrutierend» Google-Maps
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
135-8550 Koto-ku
JapanRekrutierend» Google-Maps
Seoul National University Hospital
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Asan Medical Center
138-736 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
4200-072 Porto
PortugalRekrutierend» Google-Maps
Hospital Universitari Vall d Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Hospital Clinic i Provincial de Barcelona
08036 Barcelona
SpainRekrutierend» Google-Maps
Clinica Universidad de Navarra
31008 Pamplona
SpainRekrutierend» Google-Maps
Hospital Universitario 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps
Istituto Oncologico della Svizzera Italiana
6500 Bellinzona
SwitzerlandRekrutierend» Google-Maps
Centre Hospitalier Universitaire Vaudois
1011 Lausanne
SwitzerlandRekrutierend» Google-Maps
Kantonsspital Sankt Gallen
9007 Sankt Gallen
SwitzerlandRekrutierend» Google-Maps
National Taiwan University Hospital
10002 Taipei
TaiwanRekrutierend» Google-Maps
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
33305 Taoyuan
TaiwanRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

Evaluate the safety and tolerability of AMG 509 in adult participants and determine the

maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Ein-/Ausschlusskriterien

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.

- Parts 4A and 4B:

1. Participants with histologically or cytologically confirmed mCRPC who have

received no or 1/2 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).

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). Participants on a stable bisphosphonate or denosumab regimen for

>= 30 days prior to enrollment are eligible.

- 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.

Studien-Rationale

Primary outcome:

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:

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. PSA decline of at least 50% from baseline at 12 weeks (Time Frame - Week 12):
To evaluate preliminary anti-tumor activity of AMG 509

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

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

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

12. 6 month radiographic PFS (Time Frame - 6 months):
To evaluate preliminary anti-tumor activity of AMG 509

13. 1, 2, and 3-year radiographic PFS (Time Frame - Year 1, 2, and 3):
To evaluate preliminary anti-tumor activity of AMG 509

14. 1, 2, and 3-year overall survival (OS) (Time Frame - Year 1, 2, and 3):
To evaluate preliminary anti-tumor activity of AMG 509

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

16. Rate of circulating tumor cells (CTC) conversion (Time Frame - 3 years):
To evaluate preliminary anti-tumor activity of AMG 509

17. 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.

18. 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.

19. 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.

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

21. 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.

22. 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.

Studien-Arme

  • 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 1/2 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

Geprüfte Regime

  • AMG 509 (xaluritamig):
    AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
  • Abiraterone:
    Abiraterone administered as oral tablets.
  • Enzalutamide:
    Enzalutamide administered as oral tablets.

Quelle: ClinicalTrials.gov


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