Very High Response Rate Seen in Phase III Advanced Prostate Cancer Study

Male patients with advanced prostate cancer had a 97% response rate to relugolix (Relumina), a gonadotropin-releasing hormone (GnRH) receptor antagonist, in the phase III HERO study, meeting the primary end point of the study. The trial also met all 6 of its key secondary end points, according to a press release from Myovant Sciences.

The positive study results will be the foundation for a New Drug Application (NDA) submission to the FDA. Additionally, these results will support regulatory submissions in Europe and Japan, in the future.

A response rate of 96.7% (95% CI, 94.9%-97.9%) was achieved in men treated with oral relugolix who had testosterone suppression down to castrate levels (≤50 ng/dL) that was sustained from week 5 through week 48. This was compared with the 88% suppression rate achieved by patients treated with leuprolide acetate (Lupron). The difference seen between the 2 groups was 7.9% (95% CI, 4.1%-11.8%).

In addition, relugolix demonstrated superiority in 5 of the secondary end points, compared with leuprolide acetate. Relugolix specifically suppressed testosterone levels at day 4 and 15, suppressed prostate-specific antigen (PSA), and suppressed follicle-stimulating hormone (FSH) at week 24 (P<.0001). After initiation of relugolix, there was no testosterone flare and mean testosterone levels normalized within 90 days of treatment discontinuation.

&ldquo;With the exciting results from the HERO study demonstrating the potential of relugolix to provide unique benefits compared to leuprolide, we look forward to submitting an NDA to the FDA. We are now closer to our goal of bringing a precision oral medicine to the broad spectrum of men with advanced prostate cancer,&rdquo; said Lynn Seely, MD, president and CEO, Myovant Sciences, in the press release.

In the phase III randomized, open-label, parallel-group efficacy and safety study, 1100 patients with androgen-sensitive advanced prostate cancer requiring at least 1 year of continuous androgen deprivation therapy (ADT) were randomized 2:1 to a single-loading dose of oral relugolix at 360 mg followed by 120 mg once daily or leuprolide acetate 22.5 mg 3-month depot subcutaneous or intramuscular injection. Patients attended monthly visits for investigators to assess serum testosterone and PSA. Over the course of the study, investigators also monitored adverse events, physical examinations, vital signs, 12-lead electrocardiograms, and clinical laboratory tests to assess safety.

The primary end point of the study was sustained castration rate defined as the cumulative probability of testosterone suppression to &le;50 ng/dL. Key secondary end points included castration rate by visit, profound castration rate, PSA, PSA response rate, time to PSA progression, and quality of life. The study also evaluated the QoL total score and each subdomain score, castration resistance-free survival, composite of safety, the pharmacokinetics of relugolix, testosterone recovery, and sustained profound castration rate. Additionally, blood samples were collected to assess serum concentrations of luteinizing hormone, follicle-stimulating hormone, dihydrotestosterone, and sex hormone-binding globulin.

Patients included in the HERO study had a histologically or cytologically confirmed diagnoses of adenocarcinoma of the prostate and were good candidates for 1 year on continuous ADT, according to investigator opinion. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of initial screening and at baseline; at their screening visits, patients were also required to have a serum testosterone level of &ge;150 ng/dL and a serum PSA concentration of >2.0 ng/mL (2.0 &mu;g/L).

Individuals who required chemotherapy or surgery, based on investigator opinion, were excluded from the study. Patients were also excluded due to brain metastases, history of surgical castration or having been treated with received gonadotropin-releasing hormone analog or another form of ADT or having had prior systemic cytotoxic treatment for prostate cancer.

Of the 1100 study participants, about 380 had advanced prostate cancer, to back the secondary end point of time to castration resistance. Approximately 430 patients had metastatic disease to support the castration resistance-free survival end point. Data for this end point is expected in the third quarter of 2020. Additionally, the study included 138 Chinese patients to supports its registration in China. These patients experienced a screening period, a 48-week treatment period, and a follow-up period. For patients being monitoring for safety concerns, additional follow-up visits were sometimes required.

The incidence of adverse events related to treatment with relugolix (92.9%) was comparable to those seen with leuprolide acetate (93.5%). Reportedly, 3.5% of patients in the relugolix group discontinued treatment due to toxicity. In the leuprolide acetate arm, 2.6% of men discontinued treatment. The most common adverse events among participants in the relugolix group were fatigue, hot flashes, diarrhea, constipation, and arthralgia, which occurred in 10% of the group. There were major adverse events in both groups, with the highest number seen in the leuprolide acetate, at 6.2% compared with 2.9% in the relugolix group. These events were cardiovascular toxicities, like, non-fatal stroke, non-fatal myocardial infarction, and all-cause mortality.

Relugolix is not FDA approved for the treatment of any malignancy, however, the drug has shown efficacy in women&rsquo;s health for the treatment of conditions like uterine fibroids, as seen in the LIBERTY 1 and 2 studies, and endometriosis, as shown in the SPIRIT 1 and 2 studies. Based on the data from the phase III HERO study, however, Myovant Sciences plans to submit an NDA by the second quarter of 2020.

&ldquo;An oral gonadotropin-releasing hormone, or GnRH, antagonist for advanced prostate cancer has been an aspiration for many years. If approved, relugolix would become the first-of-its-kind oral option for men with advanced prostate cancer,&rdquo; said Neal Shore, MD, medical director, and HERO Program Steering Committee member, Carolina Urologic Research Center, in a statement.

Reference:

Myovant Sciences Announces 97% Response Rate in Positive Phase 3 HERO Study of Once-Daily, Oral Relugolix in Men with Advanced Prostate Cancer [press release]. Basel, Switzerland: Myovant Sciences; November 19, 2019. https://bit.ly/2Opo7HH . Accessed November 19, 2019.