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JOURNAL ONKOLOGIE – STUDIE

Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With mCRPC

Rekrutierend

NCT-Nummer:
NCT03792841

Studienbeginn:
Februar 2019

Letztes Update:
12.04.2021

Wirkstoff:
AMG 160, Pembrolizumab, Etanercept, Immunomodulating Agent

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 23)

Alle anzeigen

Studien-Informationen

Detailed Description:

This is a phase I, first-in-human study to evaluate the safety and tolerability of AMG 160; a

half-life extended (HLE) bispecific T-cell engager (BiTE®) antibody construct, alone and in

combination with pembrolizumab in subjects with metastatic castration-resistant prostate

cancer.

Ein-/Ausschlusskriterien

All Parts

Inclusion Criteria:

- Subject has provided informed consent prior to initiation of any study-specific

activities/procedures

- Subjects with histologically or cytologically confirmed mCRPC who are refractory to a

novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) 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). Progression on novel antiandrogen therapy may have occurred in the

non-metastatic CRPC setting

- Subject should have undergone bilateral orchiectomy or should be on continuous

androgen-deprivation therapy (ADT) 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 PCWG3 criteria:

PSA level >/=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,

and/or appearance of 2 or more new lesions in bone scan

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1

- Life expectancy >/=6 months

Exclusion Criteria:

- Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not

including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue

(agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for

>/= 30 days prior to randomization are eligible

- Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed

with Amgen medical monitor prior to enrollment)

- Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord

compression

- Active autoimmune disease or any other diseases requiring immunosuppressive therapy

while on study

- Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or

equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis

factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose

- Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication,

and/or symptomatic congestive heart failure (New York Heart Association > class II)

within 12 months of first dose of AMG 160

Part 2 only:

- Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher

immune-related adverse event prior to first day of dosing

- History or evidence of interstitial lung disease or active, non-infectious pneumonitis

Part 3 only:

-Evidence of active tuberculosis on chest radiograph within 3 months prior to the first

dose of investigational product

Part 6 only:

Subjects are excluded from this cohort if any of the following additional criteria apply:

- Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg

PO QD.

- Subjects with latent or active tuberculosis at screening

Studien-Rationale

Primary outcome:

1. Number of participants with dose-limiting toxicity (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

2. Number of participants with treatment-emergent adverse events (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

3. Number of participants with treatment-related adverse events (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

4. Number of participants with clinically significant changes in vital signs (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

5. Number of participants with clinically significant changes in electrocardiogram (ECG) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

6. Number of participants with clinically significant changes in clinical laboratory tests (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

Secondary outcome:

1. Subject incidence of changes in pharmacokinetics - maximum serum concentration (Cmax) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

2. Objective response (OR) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

3. Prostate-specific antigen (PSA) response (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

4. Duration of response (DOR) (radiographic and PSA) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

5. Change in time to progression (radiographic and PSA) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

6. 1, 2 and 3-year overall survival (OS) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

7. Other PCWG3-recommended endpoints - time to symptomatic skeletal events (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

8. Subject incidence of changes in pharmacokinetics - minimum serum concentration (Cmin) (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

9. Subject incidence of changes in pharmacokinetics - area under the concentration-time curve (AUC) over the dosing interval (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

10. Subject incidence of changes in pharmacokinetics - administration including accumulation following multiple dosing (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

11. Subject incidence of changes in pharmacokinetics - half-life (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

12. Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

13. Other PCWG3-recommended endpoints - hemoglobin (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

14. Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

15. Other PCWG3-recommended endpoints - urine N-telopeptide (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

16. Other PCWG3-recommended endpoints alkaline phosphatase [total, bone] (Time Frame - Up to 3 years):
Parts 1, 2, 3, 4, 5, and 6 of the study

Studien-Arme

  • Experimental: AMG 160 Treatment
    Part 1: AMG 160 is administered intravenously at different dose levels.
  • Experimental: AMG 160 + Pembrolizumab
    Part 2: AMG 160 is administered intravenously at different dose levels. Pembrolizumab will be administered intravenously.
  • Experimental: AMG 160 + Etanercept Prophylaxis
    Part 3: AMG 160 is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.
  • Experimental: AMG 160 24 hr monitoring
    Part 4: AMG 160 is administered intravenously at RP2D/MTD with 24-hour monitoring.
  • Experimental: AMG 160 Outpatient Cohort
    Part 5: AMG 160 is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.
  • Experimental: AMG 160 + Immunomodulating Agent
    Part 6: AMG 160 is administered intravenously at RP2D/MTD levels. Immunomodulating agent will be administered orally.

Geprüfte Regime

  • AMG 160 (PSMA Targeted Therapy):
    Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
  • Pembrolizumab (PD-1 inhibitor):
    Combined with AMG 160 for investigational treatment of mCRPC
  • Etanercept (TNF-alpha inhibitor):
    Prophylaxis for AMG 160-related cytokine release syndrome.
  • Immunomodulating Agent (Immunomodulator):
    Prophylaxis for AMG 160-related cytokine release syndrome

Quelle: ClinicalTrials.gov


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