ARAMON, a phase 2 open-label trial of darolutamide monotherapy in patients with biochemical recurrence or oligometastatic castration-sensitive prostate cancer after radical prostatectomy or primary radiotherapy

Background and objective: Darolutamide is an androgen receptor inhibitor (ARI) with low blood–brain barrier penetration, potentially resulting in low reactive testosterone increases and less feminizing adverse events (AEs). In the phase 2, open-label, ARAMON trial (NCT05526248), change in serum testosterone after darolutamide monotherapy was investigated in patients with biochemical recurrence (BCR) or oligometastatic castration-sensitive prostate cancer (CSPC). Methods: Eligible patients had CSPC, prostate-specific antigen (PSA) ≥0.2 ng/mL after radical prostatectomy or ≥2 ng/mL after primary radiotherapy, PSA doubling time ≤20 months, <5 asymptomatic metastatic lesions, and serum testosterone >150 ng/dL. Patients received darolutamide 600 mg twice daily for 52 weeks. Primary endpoint was change in serum testosterone from baseline to week 12. Secondary endpoints included testosterone change from baseline to weeks 24 and 52, PSA response, and safety. Key findings and limitations: At baseline (n = 23), median (interquartile range) age was 74 years (67–79) and PSA 6.0 ng/mL (3.9–9.1). Mean percent increase in serum testosterone from baseline was 53% at week 12 and 48% at week 52. At week 52, 65% of patients had PSA <0.2 ng/mL. Darolutamide had a favorable safety profile. Most AEs were grade 1/2, including feminizing AEs, occurring mainly during the first 6 months. Trial limitations include a single-arm, open-label design and small sample size. Conclusions and clinical implications: In patients with CSPC, darolutamide monotherapy moderately increased testosterone from baseline to week 12, remaining stable through week 52. High PSA response rates were observed, and the safety profile was consistent with those expected with ARI monotherapy. Clinical trial registration: ClinicalTrials.gov identifier: NCT05526248.