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Clinical Trial
. 2024 Jun 3;30(11):2384-2392.
doi: 10.1158/1078-0432.CCR-23-3636.

A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer

Kunal B Desai  1 , Anthony V Serritella  2 , Walter M Stadler  1 , Peter H O'Donnell  1 , Randy F Sweis  1 , Russell Z Szmulewitz  1
Affiliations
Clinical Trial

A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer

Kunal B Desai et al. Clin Cancer Res. .

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 and methods: 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.

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Figures

Figure 1:
Figure 1:
Day 28 concentration (μg/mL) of Enzalutamide + Metabolite by cohort
Figure 2:
Figure 2:
Swimmer’s plot showing all patients on trial
Figure 3:
Figure 3:
Percentage (%) decline in PSA value from baseline to 12 weeks or later
See this image and copyright information in PMC

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