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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)

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

Ishibashi Hideyasu

GlaxoSmithKline K.K.

Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan

jp.gskjrct@gsk.com

Ishibashi Hideyasu

GlaxoSmithKline K.K.

Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan

+81-120-561-007

jp.gskjrct@gsk.com

Recruiting

June. 11, 2025

Interventional

randomized controlled trial

open(masking not used)

dose comparison control

parallel assignment

treatment purpose

- 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.

- 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.

Male

metastatic castration-resistant prostate cancer

GSK5458514

- 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

- 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

+81-3-3520-0111

May. 14, 2025

No

Canada/France/Spain/United States