Clinical Trial Summary : 20180101
Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects with mCRPC FDA Regulated: Yes

This study is currently recruiting participants.
Verified by Amgen, July 2020

Sponsored by: Amgen
Information provided by: Amgen

Purpose

A study to evaluate the safety and tolerability of AMG 160 and in combination with pembrolizumab in adult subjects with metastatic castration-resistant prostate cancer (mCRPC), and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).


Condition Intervention Phase
Metastatic Castration-resistant Prostate Cancer
Prostate cancer
Drug: AMG 160
Drug: Pembrolizumab
Drug: Etanercept
Drug: Outpatient Oncology Center
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
No Masking: true
Official Title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen Half-life Extended Bispecific T-cell Engager AMG 160 in Subjects With Metastatic Castration-resistant Prostate Cancer


Further study details as provided by Amgen

Primary Outcome Measures:
  • Number of participants with dose-limiting toxicity [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Number of participants with treatment-emergent adverse events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Number of participants with treatment-related adverse events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Number of participants with clinically significant changes in vital signs [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Number of participants with clinically significant changes in electrocardiogram (ECG) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Number of participants with clinically significant changes in clinical laboratory tests [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

Secondary Outcome Measures:
  • Subject incidence of changes in pharmacokinetics - maximum serum concentration (Cmax) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Objective response (OR) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

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

  • Duration of response (DOR) (radiographic and PSA) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Change in time to progression (radiographic and PSA) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • 1, 2 and 3-year overall survival (OS) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints - time to symptomatic skeletal events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

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

  • 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 and 4 of the study

  • Subject incidence of changes in pharmacokinetics - administration including accumulation following multiple dosing [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Subject incidence of changes in pharmacokinetics - half-life [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints - hemoglobin [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints - urine N-telopeptide [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

  • Other PCWG3-recommended endpoints alkaline phosphatase [total, bone] [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3 and 4 of the study

Estimated Enrollment: 180
Study Start Date:2019 February DDDD Study Start Date Type: Actual

Estimated Study Completion Date: August 2024
Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: AMG 160 Treatment
Part 1: AMG 160 is administered intravenously at different dose levels.
Drug: AMG 160
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
Experimental: AMG 160 + Pembrolizumab
Part 2: AMG 160 is administered intravenously at different dose levels.
Pembrolizumab will be administered intravenously at a dose of 200 mg.
Drug: AMG 160
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
Drug: Pembrolizumab
Combined with AMG 160 for investigational treatment of mCRPC
Other Name: PD-1 inhibitor
Experimental: AMG 160 + Etanercept Prophylaxis
Part 3: AMG 160 is administered intravenously at RP2D/MTD levels.
Etanercept will be administered subcutaneously at a dose of 50 mg in cycle 1 only.
Drug: Etanercept
Prophylaxis for AMG 160-related cytokine release syndrome.
Other Name: TNF-alpha inhibitor
Experimental: AMG 160 Outpatient Center
Part 4: AMG 160 is administered intravenously at RP2D/MTD in an oncology outpatient center up to 48 hours.
Drug: Outpatient Oncology Center
Outpatient administration of AMG 160 for close monitoring of AMG 160-related safety events.

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.


Eligibility

Ages Eligible for Study:  18 Years and older
Genders Eligible for Study:  Male
Gender Based: 
Gender Eligibility Description: 
Accepts Healthy Volunteers:  No

Criteria

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

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 requiringmedication, and/or symptomatic congestive heart failure (New York HeartAssociation > 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 pneumonitisPart 3 only:
• Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product


Contacts and Locations

Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

 Show 12 Study Locations

Sponsors and Collaborators
Amgen
Oversight
Is FDA Regulated Intervention: Yes
U.S. FDA IND/IDE Study: Yes

Investigators
Study Director: MD   Amgen

More Information

http://www.amgentrials.com

No publications provided

Responsible Party:
Other Study ID Numbers: 20180101
Health Authority:
U.S. FDA-regulated Drug Yes
U.S. FDA-regulated Device No
Post Prior to Approval/Clearance
Pediatric Postmarket Surveillance
Product Exported From U.S.

Keywords provided by Amgen:

AMG 160
HLE-BiTE®
mCRPC
Metastatic Castration-resistant Prostate Cancer
Prostate cancer
PSMA
BiTE®
Bispecific T-Cell engager
Immunotherapy
Immuno-oncology
Immunooncology
Solid tumor
PSMA Targeted Therapy