Clinical Trials /

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

NCT03792841

Description:

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).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With mCRPC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 20180101
  • NCT ID: NCT03792841

Conditions

  • Metastatic Castration-resistant Prostate Cancer
  • Prostate Cancer

Interventions

DrugSynonymsArms
AMG 160PSMA Targeted TherapyAMG 160 + Pembrolizumab
PembrolizumabPD-1 inhibitorAMG 160 + Pembrolizumab
EtanerceptTNF-alpha inhibitorAMG 160 + Etanercept Prophylaxis
Outpatient Oncology CenterAMG 160 Outpatient Center

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
AMG 160 TreatmentExperimentalPart 1: AMG 160 is administered intravenously at different dose levels.
  • AMG 160
AMG 160 + PembrolizumabExperimentalPart 2: AMG 160 is administered intravenously at different dose levels. Pembrolizumab will be administered intravenously at a dose of 200 mg.
  • AMG 160
  • Pembrolizumab
AMG 160 + Etanercept ProphylaxisExperimentalPart 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.
  • Etanercept
AMG 160 Outpatient CenterExperimentalPart 4: AMG 160 is administered intravenously at RP2D/MTD in an oncology outpatient center up to 48 hours.
  • Outpatient Oncology Center

Eligibility Criteria

        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

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicity
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study

Secondary Outcome Measures

Measure:Subject incidence of changes in pharmacokinetics - maximum serum concentration (Cmax)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Objective response (OR)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Prostate-specific antigen (PSA) response
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Duration of response (DOR) (radiographic and PSA)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Change in time to progression (radiographic and PSA)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:1, 2 and 3-year overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints - time to symptomatic skeletal events
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Subject incidence of changes in pharmacokinetics - minimum serum concentration (Cmin)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Subject incidence of changes in pharmacokinetics - area under the concentration-time curve (AUC) over the dosing interval
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Subject incidence of changes in pharmacokinetics - administration including accumulation following multiple dosing
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Subject incidence of changes in pharmacokinetics - half-life
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH]
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints - hemoglobin
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints - urine N-telopeptide
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study
Measure:Other PCWG3-recommended endpoints alkaline phosphatase [total, bone]
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2, 3 and 4 of the study

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • 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

Last Updated

July 23, 2020