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)

GlaxoSmithKline K.K.0 个研究点目标入组 7 人开始时间: 待定最近更新: 2025年5月20日

试验速览

暂无简介。

•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 <-
•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.

Incidence of DLTs per dose level in the DLT observation period

时间窗: DLT observation period

Incidence of DLTs per dose level

Incidence, and severity of AEs/SAEs and AEs leading to dose modifications, e.g. interruptions and drug discontinuations

Incidence and severity of AEs/SAEs and AEs leading to dose modifications (e.g., interruptions and drug discontinuations)

发起方

GlaxoSmithKline K.K.