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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04740034
• Other study ID #: TNB585.001
• Secondary ID: 20210249
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 29, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• AMG 340
AMG 340 is a bispecific antibody targeting prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T-cells

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Tennessee Oncology	Nashville	Tennessee
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Thomas Jefferson University - Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	UCSF	San Francisco	California
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with Dose-limiting toxicities (DLT)		21 days
Primary	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
Primary	Maximum Observed Plasma Concentration of AMG 340		3 weeks
Primary	Time to Maximum Observed Plasma Concentration of AMG 340		3 weeks
Primary	Area under the concentration-time curve within a dosing interval (AUC0-t) of AMG 340		3 weeks
Secondary	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
Secondary	Overall survival (OS)		24 months
Secondary	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
Secondary	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
Secondary	Percentage of subjects that achieve a reduction of = 30% in prostate specific antigen (PSA30)		24 months
Secondary	Percentage of subjects that achieve a reduction of = 50% in prostate specific antigen (PSA50)		24 months
Secondary	Percentage of subjects that achieve a reduction of = 70% in prostate specific antigen (PSA70)		24 months
Secondary	Percentage of subjects that achieve a reduction of = 90% in prostate specific antigen (PSA90)		24 months
Secondary	Time to progression		24 months
Secondary	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
Secondary	Prostate specific antigen (PSA) DOR based on PSA50		24 months
Secondary	Time to symptomatic skeletal events (SSE)		24 months