The second phase of a study evaluating N-terminal domain androgen receptor inhibitor masofaniten (EPI-7386) in combination with antiandrogen Xtandi (enzalutamide) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naïve to second-generation antiandrogens has been launched, according to a Sept. 18 news release from clinical-stage pharmaceutical company ESSA Pharma Inc.
The overall study began in December of 2021, according to its listing on clinicaltrials.gov, and its second phase will be a two-arm, randomized, open-label study of approximately 120 participants evaluating the safety, tolerability and preliminary efficacy of masofaniten.
Participants will be randomized two-to-one to receive 600 mg of masofaniten twice daily and 160 mg of Xtandi once daily or a 160 mg daily single-agent dose of Xtandi, according to the news release, which stated that patients may remain on treatment as long as they are tolerating treatment without disease progression.
Masofaniten, ESSA explained in the news release, is a “highly selective, oral, small molecule inhibitor of the N-terminal domain (NTD) of the androgen receptor (AR). Masofaniten’s unique mechanism of action disrupts the AR signaling pathway, the primary pathway that drives prostate cancer growth, by selectively binding to the NTD, a region of the AR that is not currently targeted by other therapies.”
At the European Society of Medical Oncology Congress (ESMO) from Oct. 20 to 24 in Madrid, ESSA will present updated results from the first four cohorts of participants in the phase 1 dose escalation phase of the study in a poster presentation.
“Initiation of the randomized phase 2 portion of this study investigating the combination of masofaniten and (Xtandi) a significant milestone for ESSA and we look forward to reporting updated results from the phase 1 dose equilibration portion of the study next month at ESMO 2023,” Dr. David Parkinson, president and CEO of ESSA, said in the news release.
“The favorable safety profile observed to date with the combination has led the safety review board to agree that we can proceed forward into the head-to-head comparison portion of the study with the dose regimen studied in cohort 4 as our recommended phase 2 dose. We look forward to further elucidating the Combination’s potential to improve long-term clinical benefit for patients with mCRPC. We plan to provide guidance for timing of the public disclosure of initial data once the phase 2 portion has been underway for several months.”
Earlier this year, when discussing results from a phase 1 study evaluating masofaniten as a monotherapy among patients whose tumors have progressed on standard-of-care therapies during the 16th Annual Interdisciplinary Prostate Cancer Congress and Other Genitourinary Malignancies, medical oncologist Dr. Matthew Dallos of Memorial Sloan Kettering Cancer Center in New York City reported that the drug was well-tolerated, with side effects including mild gastrointestinal toxicity and fatigue.
As reported by CURE’s sibling publication OncLive, among the 17 patients remained on study for more than a year, nine had measurable disease at baseline and decreases in measurable disease were observed in seven of those patients.
Treatment was masofaniten as a monotherapy was found to be safe, well-tolerated and “achieved target clinical exposures and showed preliminary signals of antitumor activity in heavily-pretreated mCRPC,” according to the authors of a study evaluating the trial results published in February in the Journal of Clinical Oncology.
The Food and Drug Administration granted Fast Track designation to masofaniten in 2020 for the development of treatment of adult male patients with mCRPC resistant to standard-of-care treatment.
Prostate cancer is the second most common cancer among American men after skin cancer, according to the American Cancer Society, which estimated that there will be approximately 288,300 new cases of prostate cancer and approximately 34,700 deaths from prostate cancer in the United States in 2023.
Approximately one out of every eight men in America will receive a diagnosis of prostate cancer during his life and approximately one out of every 41 men will die of prostate cancer, the second leading cancer death among American men behind lung cancer, the American Cancer Society reported.
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