Clinical trial NCT04740034: A Study of AMG 340 in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: Prostate specific membrane antigen
PSMA
Prostate cancer
Metastatic
Castrate-resistant
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-02-05
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: From enrollment up to and including a maximum of 90 days after last dose of AMG 340; median (min, max) duration was 4.3 (0.5, 27.1) months
measure: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
timeFrame: Up to approximately Day 21
measure: Median Concentration of AMG 340
timeFrame: Cohorts 1-5: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 8, and 10; Cohorts 6-10: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 5 (pre-dose to 6 hours post-dose), 6, 7, 8 (pre-dose to 6 hours post-dose), 9, 10
Secondary outcomes:
measure: Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 24 months
measure: Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
timeFrame: Up to approximately 24 months
measure: Radiographic PFS (rPFS)
timeFrame: Up to approximately 24 months
measure: Percentage of Participants With rPFS at 6 Months
timeFrame: 6 months
measure: Percentage of Participants With a 30% Reduction From Baseline in PSA (PSA30)
timeFrame: Up to approximately 24 months
measure: Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)
timeFrame: Up to approximately 24 months
measure: Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)
timeFrame: Up to approximately 24 months
measure: Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR) Per RECIST 1.1
timeFrame: Up to approximately 24 months
measure: Number of Participants With Symptomatic Skeletal Events (SSE)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Sidney Kimmel Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: