A Study of AMG 340 in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma

Study Overview
=================
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.

Official Title
-----------------
A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AMG 340, a Bispecific Antibody Targeting PSMA in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma

Conditions
-----------------
Metastatic Castration-resistant Prostate Cancer

Intervention / Treatment
-----------------
* Drug: AMG 340


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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). Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified. | Drug: AMG 340<br>* AMG 340 is a bispecific antibody targeting prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T-cells<br>|
| Experimental: Dose Expansion<br>An expansion cohort in subjects with mCRPC will be enrolled after RP2D is established. | Drug: AMG 340<br>* AMG 340 is a bispecific antibody targeting prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T-cells<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Dose-limiting toxicities (DLT) |  | 21 days | 
| Number of subjects with treatment-emergent adverse events (TEAEs) | Includes TEAEs, treatment-related TEAEs, serious TEAEs, and clinically significant changes from baseline in vital signs and clinical laboratory tests. | From screening until 90 Days after end of treatment | 
| Maximum Observed Plasma Concentration of AMG 340 |  | 3 weeks | 
| Time to Maximum Observed Plasma Concentration of AMG 340 |  | 3 weeks | 
| Area under the concentration-time curve within a dosing interval (AUC0-t) of AMG 340 |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity by objective response rate (ORR) | Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment | 24 months | 
| Overall survival (OS) |  | 24 months | 
| Anti-tumor activity by progression free survival (PFS) | Progression-free survival time is defined as the time from the first dose of AMG 340 to progression or death, whichever occurs first | 24 months | 
| Anti-tumor activity by progression free survival (PFS) at 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 | 6 months | 
| 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 | 
| 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) | 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 | 24 months | 
| Prostate specific antigen (PSA) DOR based on PSA50 |  | 24 months | 
| Time to symptomatic skeletal events (SSE) |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate specific membrane antigen, PSMA, Prostate cancer, Metastatic, Castrate-resistant