A Study of GSK5458514 Administered Alone or In Combination With Other Anti-Cancer Agents in Participants With Prostate Cancer

June 17, 2026 updated by: GlaxoSmithKline

A Phase 1/2 First-Time-In-Human, Open-Label, Multicenter, Dose Escalation and Expansion Study of GSK5458514 PSMA Targeting T Cell Engager Alone or in Combination With Other Anti-Cancer Agents in Adult Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

The goal of the study is to evaluate how safe and how well the body handles GSK5458514 when administered in participants with prostate cancer. The study will be conducted in two parts - Part 1 (dose escalation phase) and Part 2 (dose expansion phase).

Study Overview

Status

Status

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

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 (Estimated)

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.
85

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 2
  • 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 Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ramy Saleh
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • April Rose
        • Contact:
        • Contact:
  • France
      • Lyon, France, 69373
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Armelle Vinceneux
      • Villejuif, France, 94805
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Yohann Loriot
        • Contact:
        • Contact:
  • Japan
      • Kanagawa, Japan, 232-0024
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Takashi Kawahara
      • Tokyo, Japan, 104-0045
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Tatsunori Shimoi
      • Tokyo, Japan, 135-8550
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yuji Miura
  • Spain
      • Badajoz, Spain, 06080
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marta Gonzalez Cordero
      • Barcelona, Spain, 08023
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Tatiana Hernandez
        • Contact:
        • Contact:
      • Madrid, Spain, 28040
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bernard Doger
      • Madrid, Spain, 28050
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Emiliano Calvo Aller
        • Contact:
        • Contact:
      • Málaga, Spain, 29010
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lucia Oliva Fernandez
      • Pozuelo de AlarcOn Madr, Spain, 28223
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • VALENTINA BONI
        • Contact:
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Principal Investigator:
          • Yousef Zakharia
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Gerald Falchook
        • Contact:
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Daniel Petrylak
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dan Childs
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bruno Fang
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Benjamin Garmezy

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Provide signed informed consent. Participants must be capable of providing informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • Male participants ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the ICF.

Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 195 days, after the last dose of study intervention:

Refrain from donating sperm

PLUS either:

Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.

OR

Must agree to use contraception as detailed below:

Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.

  • Participants with mCRPC:

    • Histologically or cytologically confirmed adenocarcinoma of the prostate
    • Metastatic disease diagnosed either by radiologic imaging (Positron emission tomography [PET]- Computed tomography [CT]) and/or regular CT and/or Magnetic resonance imaging (MRI) and/or bone scan
    • Castration-resistant status as per PCWG3 criteria
  • Has prior novel anti-androgen receptor therapy failure and had treatment failure with 1-2 taxane-based chemotherapy regimens including for metastatic hormone sensitive prostate cancer.
  • Has (1) at least 1 soft tissue target lesion per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) OR (2) if Non-Target soft tissue disease only per PCWG3-modified RECIST 1.1, may be included if a rise in PSA on 2 successive determinations at least 1 week apart (the most recent screening measurement must have been ≥ 2 ng/mL) with testosterone levels <50 ng/dL, OR (3) bone disease defined by PCWG3 (2 or more lesions on bone scan at screening), as determined by the investigator.
  • Documented disease progression on most recent systemic therapy defined by fulfilling at least 1 of the PCWG3 criteria
  • Have serum testosterone <50 ng/dL (<1.7 nM). Patients must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a GnRH agonist or antagonist; this therapy must have been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1, with no deterioration in the 2 weeks before step-up treatment period Day 1.
  • Have supplied tumor tissue from a newly obtained biopsy or archival tumor tissue for retrospective detection of Prostate-specific membrane antigen (PSMA) expression and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue preferably taken after the completion of the participant's last line of therapy prior to the first dose of study drug is acceptable.
  • Participants must have adequate organ function

Exclusion Criteria:

  • Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any histology different from adenocarcinoma.
  • History of central nervous system (CNS) metastases or leptomeningeal disease.

  • Diagnosis of invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years, except as noted below:

    • History of an invasive malignancy for which the participant was definitively treated, and in which the participant has been disease free for at least 2 years, and which, in the opinion of the principal investigator and medical monitor, is not expected to affect the evaluation of the effects of the study intervention on the currently targeted disease under study
    • Curatively treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and/or in situ breast cancer may be enrolled
    • • Has ongoing adverse reaction(s) from prior therapy that have not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, excluding [e.g., alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy], or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
  • Confirmed history or recurrent autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
  • Has evidence of interstitial lung disease, non-infectious pneumonitis, and/or a history of interstitial lung disease, non-infectious pneumonitis that required steroid .
  • Any anti-cancer therapy or prior systemic biologic therapy, including immunotherapy within 4 weeks of start dose.
  • Prior PSMA radionuclide therapy within 2 months prior to GSK5458514 unless participant received <2 cycles.
  • Prior PSMA-Chimeric antigen receptor T cell therapy (CAR-T) cell therapy and PSMA (T cell engager) TCE/ Bispecific T cell engagers (BiTE) or other prostate Tumor-associated antigens (TAA) specific T cell engager (TCE).
  • Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
  • Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • History of severe neurological or psychiatric disorder, including epilepsy, dementia, or major depression deemed to interfere with study assessments.
  • Has had any major surgery (such as craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks prior to first dose of study intervention.
  • Serious infections within 4 weeks prior to the first dose, including but not limited to infectious complications, bacteremia, severe pneumonia treated with IV antibiotics for ≥2 weeks; active infections with therapeutic IV antibiotics within 2 weeks prior to the first dose or oral antibiotics within 1 week prior to the first dose. Participants who are receiving or have received prophylactic antibiotics (e.g., prophylaxis against urinary infections) are allowed.

Liver safety exclusion criteria:

  • Has an Alanine aminotransferase (ALT) value >2.5x upper limit of normal (ULN) or >5x ULN if documented history of liver metastases.
  • Has a total bilirubin value >1.5x ULN.
  • Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
  • Has documented presence of Hepatitis B surface antigen (HBsAg), at screening or within 3 months prior to the first dose of study intervention.
  • Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to Cycle 1 Day 1 unless the participant can meet the following criteria: NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled if a confirmatory negative HCV RNA test is obtained and the participant otherwise meets entry criteria
  • Has a positive HCV ribonucleic acid (RNA) test result at screening or within 3 months prior to the first dose of study intervention. NOTE: The HCV RNA test is optional, and participants with a negative HCV antibody test are not required to undergo HCV RNA testing as well.
  • Is unable to adhere to the protocol defined SoA, including requirements for the Follow-up Period of the study, study procedures, restrictions, and requirements as determined by the investigator.

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: 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: Part 1: Dose escalation of GSK5458514 monotherapy
Drug: GSK5458514
GSK5458514 will be administered.
Experimental: Part 2: Dose expansion of GSK5458514 monotherapy
Drug: GSK5458514
GSK5458514 will be administered.

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
Time Frame
Number of participants with dose limiting toxicities (DLTs) during DLT observation period
Time Frame: Up to 28 days
Up to 28 days
Number of participants with adverse events (AEs), serious adverse events (SAEs), by Severity
Time Frame: Up to approximately 29 months
Up to approximately 29 months
Number of participants with AEs leading to dose modifications
Time Frame: Up to approximately 29 months
Up to approximately 29 months

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
Area under concentration from 0 to t (AUC 0-t) of GSK5458514
Time Frame: Up to approximately 32 months
Up to approximately 32 months
Maximum concentration (Cmax) of GSK5458514
Time Frame: Up to approximately 32 months
Up to approximately 32 months
Time to reach maximum concentration (Tmax) of GSK5458514
Time Frame: Up to approximately 32 months
Up to approximately 32 months
Number of participants with Anti-drug antibodies (ADA) against GSK5458514
Time Frame: Up to approximately 32 months
Up to approximately 32 months
Titers of ADA against GSK5458514
Time Frame: Up to approximately 32 months
Up to approximately 32 months
Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate
Time Frame: Up to approximately 32 months
PSA50 response rate is defined as percentage of participants with a decrease of >=50% in the PSA concentration from the baseline PSA value, confirmed at least 3 weeks later.
Up to approximately 32 months
Objective Response Rate (ORR)
Time Frame: Up to approximately 32 months
ORR is defined as the percentage of participants in the ORR Evaluable set who have a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per prostate cancer working group 3 (PCWG3) guidelines as assessed by investigator.
Up to approximately 32 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.
GlaxoSmithKline

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.
June 12, 2025

Primary Completion (Estimated)

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.
October 26, 2027

Study Completion (Estimated)

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.
August 9, 2028

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).
May 22, 2025

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.
May 22, 2025

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.
May 25, 2025

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 18, 2026

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.
June 17, 2026

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.
June 1, 2026

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.
  • 223050
  • 2025-521581-10 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

IPD Sharing Time Frame

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

IPD Sharing Access Criteria

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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.

Clinical Trials on Neoplasms, Prostate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings