metastatic castration-resistant prostate cancer
Conditions
Interventions
Sponsors
Ishibashi Hideyasu
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Provide signed informed consent. - Participants with mCRPC. - 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. - Documented mCRPC disease progression on most recent systemic therapy defined by fulfilling at least 1 of the PCWG3 criteria. - Have at least 1 target lesion per 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. - 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. - ECOG performance status <-1. - Have supplied tumor tissue from a newly obtained biopsy or archival tumor tissue. - Participants must have adequate organ function.
Exclusion criteria
Exclusion criteria: - Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any histology different from adenocarcinoma. - History of CNS metastases or leptomeningeal disease. - Has ongoing adverse reaction(s) from prior therapy that have not recovered to <-Grade 1 or to the baseline status preceding prior therapy. - Confirmed history or recurrent autoimmune disease that has required systemic treatments in the 2 years prior to screening. - 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-CAR-T cell therapy and PSMA TCE/BiTE or other prostate TAA specific TCE. - History of severe neurological or psychiatric disorder, including epilepsy, dementia, or major depression deemed to interfere with study assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Incidence of DLTs per dose level in the DLT observation period - Incidence, and severity of AEs/SAEs and AEs leading to dose modifications, e.g. interruptions and drug discontinuations | — |
Secondary
| Measure | Time frame |
|---|---|
| - GSK5458514 PK parameters following IV dose administration, as data permit - Incidence and titers of ADAs against GSK5458514 - PSA50 response defined as a >-50% decline in PSA levels from baselinea - ORR per PCWG3 by investigator | — |
Countries
Canada, France, Japan, Spain, United States
Contacts
Public ContactHideyasu Ishibashi
GlaxoSmithKline K.K.
Outcome results
None listed