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).
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
Drug | Synonyms | Arms |
---|
AMG 160 | PSMA Targeted Therapy | AMG 160 + Etanercept Prophylaxis |
Pembrolizumab | PD-1 inhibitor | AMG 160 + Pembrolizumab |
Etanercept | TNF-alpha inhibitor | AMG 160 + Etanercept Prophylaxis |
Immunomodulating Agent | Immunomodulator | AMG 160 + Immunomodulating Agent |
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
Name | Type | Description | Interventions |
---|
AMG 160 Treatment | Experimental | Part 1: AMG 160 is administered intravenously at different dose levels. | |
AMG 160 + Pembrolizumab | Experimental | Part 2: AMG 160 is administered intravenously at different dose levels. Pembrolizumab will be administered intravenously. | |
AMG 160 + Etanercept Prophylaxis | Experimental | Part 3: AMG 160 is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only. | |
AMG 160 24 hr monitoring | Experimental | Part 4: AMG 160 is administered intravenously at RP2D/MTD with 24-hour monitoring. | |
AMG 160 Outpatient Cohort | Experimental | Part 5: AMG 160 is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring. | |
AMG 160 + Immunomodulating Agent | Experimental | Part 6: AMG 160 is administered intravenously at RP2D/MTD levels. Immunomodulating agent will be administered orally. | - AMG 160
- Immunomodulating Agent
|
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
- 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
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, 4, 5, and 6 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, 4, 5, and 6 of the study |
Measure: | Objective response (OR) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 of the study |
Measure: | Prostate-specific antigen (PSA) response |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 of the study |
Measure: | Duration of response (DOR) (radiographic and PSA) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 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, 4, 5, and 6 of the study |
Measure: | Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 of the study |
Measure: | Other PCWG3-recommended endpoints - hemoglobin |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 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, 4, 5, and 6 of the study |
Measure: | Other PCWG3-recommended endpoints - urine N-telopeptide |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Parts 1, 2, 3, 4, 5, and 6 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, 4, 5, and 6 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
June 7, 2021