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

Amgen

Status and phase: Terminated; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: AMG 340

Study type: Interventional

Funder types: Industry

Identifiers

NCT04740034

TNB585.001

20210249 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.

Treatment:

Drug: AMG 340

Dose Expansion

Experimental group

Description:

An expansion cohort in subjects with mCRPC will be enrolled after RP2D is established.

Treatment:

Drug: AMG 340