News
Article
Author(s):
The primary end point is 12-month radiographic progression-free survival.
RedHill Biopharma has announced the initiation of a phase 2 trial to explore the combination of opaganib (ABC294640) plus darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer (mCRPC).1
The study plans to enroll 80 patients with mCRPC.
The study will utilize the companion lipid biomarker test PCPro to select patients who may benefit from the study combination due to a poor prognosis from standard-of-care treatment. The investigators will initially identify 200 potentially eligible patients to undergo PCPro testing using a 5-mL plasma sample. Those who are PCPro-positive (estimated 40% of patients) will be randomly assigned 1:1 to receive either 600 mg darolutamide BID plus placebo (estimated n = 40) or to 600 mg darolutamide BID plus 500 mg opaganib BID (estimated n = 40).
"The approach of developing therapeutic combinations and the companion lipid biomarker, PCPro, in parallel is unique in metabolic targeting in metastatic prostate cancer, and this exciting study will test the ability of sphingosine kinase-2 (SPHK2) inhibitors, such as opaganib, to overcome resistance to ARPI treatment," said principal investigator Lisa Horvath, Chief Clinical Officer and Director of Research at Chris O'Brien Lifehouse, in the news release.1 "Cancer cells may block apoptosis (programmed cell death), an important cell-level process designed to help the body get rid of unneeded or abnormal/unhealthy cells—critical in fighting the spread of cancer. We know from our prior research that opaganib enhances androgen receptor signaling inhibitor efficacy in vitro, through simultaneous inhibition of 3 sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS), and may potentially provide the key to overcoming darolutamide resistance in men with mCRPC."
In total, the placebo-controlled, randomized study plans to enroll 80 patients with mCRPC. Patients are not eligible for enrollment if they have had prior treatment with newer, potent androgen receptor signaling inhibitors, including darolutamide, enzalutamide (Xtandi), apalutamide (Erleada), and abiraterone (Zytiga).
Patients will begin on study treatment within 7 days of randomization.
The primary end point is 12-month radiographic progression-free survival (rPFS). According to RedHill Pharma, the trial will also assess several secondary and exploratory end points.
Opaganib is an investigational oral SPHK2 selective inhibitor “targeting multiple potential indications, including several cancers, diabetes and obesity-related disorders, gastrointestinal acute radiation syndrome (GI-ARS), chemical exposure indications, COVID-19, Ebola, and other viruses as part of pandemic preparedness,” according to the company.
The drug was previously explored in mCRPC in a phase 2 study (NCT04207255) that completed last year.2 The study enrolled 69 patients with mCRPC whose tumors progressed while receiving abiraterone or enzalutamide. Participants were enrolled in the trial through the Medical University of South Carolina Hollings Cancer Center and Emory University in Atlanta, Georgia.
For the study, patients received either 250 mg or 500 mg opaganib in combination with abiraterone or enzalutamide. The primary end point was disease control status (stable disease or better) per PCWG3 criteria following 4 cycles of treatment. Second end points included overall survival, rPFS, and prostate-specific antigen progression-free survival.3
Final completion of the study was reported in July 2024.
References
1. RedHill announces initiation of phase 2 study of opaganib and darolutamide in advanced prostate cancer. News release. RedHill Biopharma Ltd. Published online and accessed February 4, 2025. https://www.redhillbio.com/news/news-details/2025/RedHill-Announces-Initiation-of-Phase-2-Study-of-Opaganib-and-Darolutamide-in-Advanced-Prostate-Cancer/default.aspx
2. Addition of opaganib to androgen antagonists in patients with mCRPC. ClinicalTrials.gov. Last updated September 25, 2024. Accessed February 4, 2025. https://clinicaltrials.gov/study/NCT04207255
3. Kucuk O, Smith C, Plasse T, et al. Phase II trial of opaganib in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide (NCT04207255). J Clin Oncol. 2021;39(suppl 6). doi:10.1200/JCO.2021.39.6_suppl.TPS19