A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer.
Clin Cancer Res
; 30(11): 2384-2392, 2024 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-38536082
ABSTRACT
PURPOSE:
The majority of patients with metastatic prostate cancer who receive androgen-deprivation therapy and androgen receptor (AR) signaling inhibitors (ARSI) progress. Activation of the glucocorticoid receptor (GR) is associated with ARSI resistance. This single-arm phase I trial assessed safety and pharmacokinetic (PK) feasibility of a combined AR antagonist (enzalutamide) and selective GR modulator (relacorilant) in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS ANDMETHODS:
This was a phase I trial (NCT03674814) of relacorilant and enzalutamide in patients with refractory mCRPC enrolled using a 6+3 design. The enzalutamide dose was kept constant at 120 mg/d with escalating doses of relacorilant based on safety and PK measures in cohorts of ≥6 patients. The primary objective was safety and establishment of pharmacologically active doses. Secondary objectives were related to antitumor activity.RESULTS:
Thirty-five patients with mCRPC were enrolled. Twenty-three were accrued across three dose cohorts in the dose-escalation phase, and 12 enrolled at the recommended phase II dose. The combination was generally well tolerated, safe, and achieved desirable enzalutamide PK. RP2D of 120 + 150 mg/d, respectively, was established. Median time on study was 2.2 months with four patients remaining on study for longer than 11 months. Four of 12 evaluable patients had a prostate-specific antigen (PSA) partial response.CONCLUSIONS:
This is the first prospective trial combining an AR antagonist and a nonsteroidal selective GR modulator. The combination was safe and well tolerated with PSA response and prolonged disease control observed in a limited subset of patients. Further prospective trials are justified to evaluate efficacy and identify predictive biomarkers of response.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Feniltiohidantoína
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Benzamidas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptores de Glucocorticoides
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Neoplasias de la Próstata Resistentes a la Castración
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Nitrilos
Límite:
Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
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Clin. cancer res
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Clinical cancer research
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article