RECRUITING

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

Conditions

Neoplasms, Prostate Metastatic castration-resistant prostate cancer (mCRPC)GSK5458514 Dose escalation Dose expansion

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

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)

Quick Facts

Study Start:2025-06-12

Study Completion:2028-08-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06990880

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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. * Have at least 1 target lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) OR if Non-Target soft tissue disease only, may be included if (1) 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 (2) bone disease defined by PCWG3 (2 or more lesions on bone scan at screening), as determined by the investigator. * Documented mCRPC 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	* 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: * 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, or current pneumonitis * 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.

Inclusion Criteria

Exclusion 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.
* 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.
* Have at least 1 target lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) OR if Non-Target soft tissue disease only, may be included if (1) 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 (2) bone disease defined by PCWG3 (2 or more lesions on bone scan at screening), as determined by the investigator.
* Documented mCRPC 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

* 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:
* 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, or current pneumonitis
* 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.

Contacts and Locations

Study Contact

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 Locations (Sites)

GSK Investigational Site

Nashville, Tennessee, 37203

United States

Collaborators and Investigators

Sponsor: 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 Registration Dates

Study Start Date2025-06-12

Study Completion Date2028-08-23

Study Record Updates

Study Start Date2025-06-12

Study Completion Date2028-08-23

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Neoplasms, Prostate