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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: AMG 340

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center
  • New York
    • New York, New York, United States, 10128
      • Icahn School of Medicine at Mount Sinai
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University - Sidney Kimmel Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	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.	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
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	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.	Up to approximately Day 21
Median Concentration of AMG 340	Blood samples for pharmacokinetics (PK) analysis were collected at specific time points. PK parameters were estimated using standard non-compartmental approaches.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	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.	Up to approximately 24 months
Overall Survival (OS)	OS was defined as the time from the date of study Day 1 until death due to any cause.	Up to approximately 24 months
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)	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.	Up to approximately 24 months
Radiographic PFS (rPFS)	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.	Up to approximately 24 months
Percentage of Participants With rPFS at 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.	6 months
Percentage of Participants With a 30% Reduction From Baseline in PSA (PSA30)	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.	Up to approximately 24 months
Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)	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.	Up to approximately 24 months
Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)	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.	Up to approximately 24 months
Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)	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.	Up to approximately 24 months
Duration of Response (DOR) Per RECIST 1.1	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.	Up to approximately 24 months
Number of Participants With Symptomatic Skeletal Events (SSE)	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.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): June 17, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Prostate cancer; Metastatic; PSMA; Prostate specific membrane antigen; Castrate-resistant
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: TNB585.001; 20210249 (Other Identifier: Amgen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No