A Study of AMG 340 in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Drug: AMG 340
- Registration Number
- NCT04740034
- Lead Sponsor
- Amgen
- Brief Summary
This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of AMG 340, a PSMA x CD3 T-cell engaging bispecific antibody, in subjects with metastatic castrate-resistant prostate cancer (mCRPC) who have received 2 or more prior lines of therapy. The study consists of 2 parts, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of AMG 340 monotherapy in subjects with mCRPC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 42
- Pathologically confirmed prostatic adenocarcinoma.
- History of metastatic disease.
- Chemically or surgically castrate.
- Subject has received at least 2 lines of systemic therapy approved for mCRPC, with disease progression on the most recent systemic therapy as defined in Prostate Cancer Working Group 3 (PCWG3) recommendations.
- Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)-infected subjects that have been cured or who are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- An Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Subject must have adequate heart, liver, bone marrow and kidney function (e.g. estimated glomerular filtration rate [eGFR] ≥ 50 mL/min, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ≤ 3 x upper limit of normal [ULN], hemoglobin [Hgb] ≥ 9 g/dL (without blood transfusion within 7 days from screening assessment), platelets ≥ 100,000 / mm^3 (without platelet transfusion within 7 days from screening assessment), absolute neutrophil count [ANC] ≥ 1500 / mm^3).
- Subject has been diagnosed with or treated for another malignancy within the past 2 years whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
- History of neuroendocrine differentiation in the subject's disease.
- Subject has a history of central nervous system (CNS) involvement by their mCRPC. Metastases stemming from bone are allowed.
- Subject has clinically significant CNS pathology.
- Subject requires chronic immunosuppressive therapy.
- Subject has a history of major cardiac abnormalities.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion AMG 340 An expansion cohort in subjects with mCRPC will be enrolled after RP2D is established. Dose Escalation AMG 340 Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
- Primary Outcome Measures
Name Time Method Area under the concentration-time curve within a dosing interval (AUC0-t) of AMG 340 3 weeks Number of subjects with treatment-emergent adverse events (TEAEs) From screening until 90 Days after end of treatment Includes TEAEs, treatment-related TEAEs, serious TEAEs, and clinically significant changes from baseline in vital signs and clinical laboratory tests.
Maximum Observed Plasma Concentration of AMG 340 3 weeks Number of subjects with Dose-limiting toxicities (DLT) 21 days Time to Maximum Observed Plasma Concentration of AMG 340 3 weeks
- Secondary Outcome Measures
Name Time Method Anti-tumor activity by objective response rate (ORR) 24 months Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
Overall survival (OS) 24 months Anti-tumor activity by progression free survival (PFS) 24 months Progression-free survival time is defined as the time from the first dose of AMG 340 to progression or death, whichever occurs first
Percentage of subjects that achieve a reduction of ≥ 30% in prostate specific antigen (PSA30) 24 months Percentage of subjects that achieve a reduction of ≥ 50% in prostate specific antigen (PSA50) 24 months Percentage of subjects that achieve a reduction of ≥ 70% in prostate specific antigen (PSA70) 24 months Anti-tumor activity by progression free survival (PFS) at 6 months 6 months Progression-free survival time is defined as the time from the first dose of AMG 340 to progression or death, whichever occurs first
Percentage of subjects that achieve a reduction of ≥ 90% in prostate specific antigen (PSA90) 24 months Time to progression 24 months Anti-tumor activity by duration of objective response (DOR) 24 months The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first
Time to symptomatic skeletal events (SSE) 24 months Prostate specific antigen (PSA) DOR based on PSA50 24 months
Trial Locations
- Locations (7)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
UCSF
🇺🇸San Francisco, California, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Thomas Jefferson University - Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Tulane Cancer Center
🇺🇸New Orleans, Louisiana, United States