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

NCT06990880 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2230502025-521581-10
• Study Type: interventional
• Target: 85
• Locations: 5 countries
• Sites: 15

Brief Summary

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).

Conditions

Neoplasms, Prostate

Keywords

Metastatic castration-resistant prostate cancer (mCRPC); GSK5458514; Dose escalation; Dose expansion

Outcome Measures

Primary Outcomes (3)

• Number of participants with dose limiting toxicities (DLTs) during DLT observation period

  Up to 28 days

• Number of participants with adverse events (AEs), serious adverse events (SAEs), by Severity

  Up to approximately 29 months

• Number of participants with AEs leading to dose modifications

  Up to approximately 29 months

Secondary Outcomes (7)

• Area under concentration from 0 to t (AUC 0-t) of GSK5458514

  Up to approximately 32 months

• Maximum concentration (Cmax) of GSK5458514

  Up to approximately 32 months

• Time to reach maximum concentration (Tmax) of GSK5458514

  Up to approximately 32 months

• Number of participants with Anti-drug antibodies (ADA) against GSK5458514

  Up to approximately 32 months

• Titers of ADA against GSK5458514

  Up to approximately 32 months

Study Arms (2)

Part 1: Dose escalation of GSK5458514 monotherapy

EXPERIMENTAL

Drug: GSK5458514

Part 2: Dose expansion of GSK5458514 monotherapy

EXPERIMENTAL

Drug: GSK5458514

Interventions

GSK5458514 DRUG

GSK5458514 will be administered.

Part 1: Dose escalation of GSK5458514 monotherapy; Part 2: Dose expansion of GSK5458514 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Denver, Colorado, 80218, United States

RECRUITING

GSK Investigational Site

Nashville, Tennessee, 37203, United States

RECRUITING

GSK Investigational Site

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

GSK Investigational Site

Lyon, 69373, France

RECRUITING

GSK Investigational Site

Villejuif, 94805, France

RECRUITING

GSK Investigational Site

Kanagawa, 232-0024, Japan

RECRUITING

GSK Investigational Site

Tokyo, 104-0045, Japan

RECRUITING

GSK Investigational Site

Tokyo, 135-8550, Japan

RECRUITING

GSK Investigational Site

Badajoz, 06080, Spain

RECRUITING

GSK Investigational Site

Barcelona, 08023, Spain

RECRUITING

GSK Investigational Site

Madrid, 28040, Spain

RECRUITING

GSK Investigational Site

Madrid, 28050, Spain

RECRUITING

GSK Investigational Site

Málaga, 29010, Spain

RECRUITING

GSK Investigational Site

Pozuelo de AlarcOn Madr, 28223, Spain

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: May 25, 2025
• Study Start: June 12, 2025
• Primary Completion (Estimated): October 26, 2027
• Study Completion (Estimated): August 9, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

ES (6); FR (2); CA (2); US (2); JP (3)