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

May 30, 2025 updated by: Amgen

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time Frame: 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.
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)
Time Frame: 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.
Up to approximately Day 21
Median Concentration of AMG 340
Time Frame: 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.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Time Frame: 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.
Up to approximately 24 months
Overall Survival (OS)
Time Frame: Up to approximately 24 months
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)
Time Frame: 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.
Up to approximately 24 months
Radiographic PFS (rPFS)
Time Frame: 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.
Up to approximately 24 months
Percentage of Participants With rPFS at 6 Months
Time Frame: 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)
Time Frame: 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.
Up to approximately 24 months
Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)
Time Frame: 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.
Up to approximately 24 months
Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)
Time Frame: 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.
Up to approximately 24 months
Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)
Time Frame: 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.
Up to approximately 24 months
Duration of Response (DOR) Per RECIST 1.1
Time Frame: 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.
Up to approximately 24 months
Number of Participants With Symptomatic Skeletal Events (SSE)
Time Frame: 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.
Up to approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: MD, Amgen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 29, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 24, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 24, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 1, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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