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

Phase 1

Terminated

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: TERMINATED

Sex: Male

Target Recruitment: 42

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.

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
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	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	An adverse event (AE) was any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. A treatment-related AE (TRAE) was defined as any TEAE flagged as possibly caused by AMG 340. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were any untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	Up to approximately Day 21	A DLT was defined as a TEAE that was not unequivocally due to the participant's underlying malignancy or other extraneous cause, and appeared within 21 days from the first dose of AMG 340. AEs considered DLTs were: * Transient (≤72 hours) grade 3 or 4 electrolyte abnormalities, hyperglycemia, nausea/vomiting/diarrhea responsive to treatment. * Alopecia, vitiligo, and grade 3 fatigue lasting \<10 days. * Grade 3 fever lasting ≤24 hours (outside CRS context). * Grade 3 lab abnormalities resolving within 72 hours (or within 7 days for certain enzymes like ALT, GGT, ALP, and lipase). * Grade 3 CRS or TLS unresolved to ≤ grade 1 within 72 hours or any grade 4 CRS/TLS. * Prolonged grade 4 neutropenia (\>5 days) or febrile neutropenia. * Grade 3 thrombocytopenia with bleeding or any grade 4 thrombocytopenia. * Grade 4 anemia. * Grade 5 adverse events. * Lymphopenia is not considered a DLT.
Median Concentration of AMG 340	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	Blood samples for pharmacokinetics (PK) analysis were collected at specific time points. PK parameters were estimated using standard non-compartmental approaches.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to approximately 24 months	OR was defined as a partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by a repeat assessment at least 4 weeks later. Participants who did not experience a confirmed PR/CR or did not have any follow-up tumor assessments were regarded as non-responders.
Overall Survival (OS)	Up to approximately 24 months	OS was defined as the time from the date of study Day 1 until death due to any cause.
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)	Up to approximately 24 months	PSA PFS was defined as the interval from study day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement. If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or unknown, PSA PFS was censored at study day 1.
Duration of Response (DOR) Per RECIST 1.1	Up to approximately 24 months	DOR was defined as the time from the date of an initial objective response per RECIST 1.1, which was subsequently confirmed, until soft-tissue progression per RECIST 1.1 or death, whichever occurred first in the absence of subsequent anti-cancer therapy. Participants who had not ended their response at the time of analysis had DOR censored at their last evaluable tumor assessment by CT/MRI scan prior to subsequent anti-cancer therapy. This endpoint only applied to participants with an objective response (CR or PR) per RECIST 1.1. No participants achieved CR or PR, therefore, no participants could be analyzed for this outcome measure.
Number of Participants With Symptomatic Skeletal Events (SSE)	Up to approximately 24 months	SSE was defined as time from study day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of AMG 340 or end of safety follow-up date, whichever was later.
Radiographic PFS (rPFS)	Up to approximately 24 months	rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.
Percentage of Participants With rPFS at 6 Months	6 months	rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.
Percentage of Participants With a 30% Reduction From Baseline in PSA (PSA30)	Up to approximately 24 months	PSA 30 was defined as a ≥ 30% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)	Up to approximately 24 months	PSA 50 was defined as a ≥ 50% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)	Up to approximately 24 months	PSA 70 was defined as a ≥ 70% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)	Up to approximately 24 months	PSA 90 was defined as a ≥ 90% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.

Trial Locations

Locations (7): UCSF
🇺🇸
San Francisco, California, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸
Denver, Colorado, United States
Florida Cancer Specialists
🇺🇸
Sarasota, Florida, 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
Tennessee Oncology
🇺🇸
Nashville, Tennessee, United States
UCSF
🇺🇸San Francisco, California, United States