Launch of ARANOTE Study Augments Development Program for Darolutamide in Prostate Cancer

Pipeline Report | <b>Pipeline Report: February 2021</b>

Darolutamide plus ADT will be evaluated versus ADT alone in patients with metastatic hormone-sensitive prostate cancer in the phase 3 ARANOTE study as part Bayer and Orion Corporation’s growing clinical development program for the oral AR inhibitor in prostate cancer.

Darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) will be evaluated versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the phase 3 ARANOTE study as part Bayer and Orion Corporation’s growing clinical development program for the oral androgen receptor (AR) inhibitor in prostate cancer.1

“[Darolutamide] has already shown in men with non-metastatic castration-resistant prostate cancer [nmCRPC] that it extends metastasis-free and overall survival,” said Scott Z. Fields, MD, Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. “Given the encouraging results that we have seen with [darolutamide] so far, it is important that we also evaluate the potential of [darolutamide] in other stages of prostate cancer that may offer men with mHSPC a new treatment option.”

In 2019, the FDA approved darolutamide for the treatment of patients with nmCRPC. The approval was based on data from the phase 3 ARAMIS trial, in which the AR inhibitor plus ADT led to a 59% reduction in the risk of metastases or death compared with placebo/ADT in this patient population (HR, 0.41; 95% CI, 0.34-0.50; 2-sided, P <.0001).2,3 Moreover, at a median follow-up of 17.9 months, the median metastasis-free survival (MFS) was 40.4 months with the addition of darolutamide versus 18.4 months with placebo/ADT.

Overall survival (OS) data, although not yet mature at the time of final MFS analysis, also showed a trend toward improvement with darolutamide. The 3-year rates of OS were 83% in the darolutamide arm versus 73% with placebo, translating to a 29% reduction in the risk of death (HR, 0.71; 95% CI, 0.50-0.99, P = .0452).

The randomized, double-blind, placebo-controlled ARANOTE study is expected to open by the end of the first quarter in 2021 and enroll approximately 555 men. Radiologic progression-free survival, measured by the time from the start of randomization to the first documentation of radiologic progressive disease or death due to any cause, will serve as the primary end point.

ARANOTE is 1 of many trials that have expanded the global development program for darolutamide, including the phase 3 ARASENS study (NCT02799602), which is evaluating darolutamide plus ADT versus docetaxel plus ADT in men with mHSPC.4 In the study, approximately 1300 patients will be randomized 1:1 to receive 600 mg of darolutamide or placebo twice daily plus standard ADT and 6 cycles of docetaxel.

Patients will be stratified at randomization for the extent of disease and for alkaline phosphatase levels.

Treatment with darolutamide and placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, or patient or physician withdrawal.

References

1. Bayer and Orion expand development program for nubeqa (darolutamide) in prostate cancer. February 8, 2021. Bayer. News release. Accessed February 17, 2021. https://bit.ly/3kgDwcL

2. Fizazi K, Shore ND, Tammela T, et al. ARAMIS: efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2019;37(suppl 7);140. doi:10.1200/JCO.2019.37.7_suppl.140

3. Fizazi K, Shore N, Tammela T, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. 2019;380(13):1235-1246. N Eng J Med. doi: 10.1056/NEJMoa1815671.

4. ODM-201 in addition to standard ADT and docetaxel in metastatic castration sensitive prostate cancer (ARASENS). ClinicalTrials.gov. Posted June 15, 2016. Updated February 21, 2021. Accessed February 18, 2021. https://clinicaltrials.gov/ct2/show/NCT02799602.