A phase 1 trial of EPI-7386 will evaluate the safety, pharmacokinetics, drug-drug interactions, and preliminary anti-tumor activity of the agent in combination with apalutamide or abiraterone acetate plus prednisone.
Trial Name: A Phase 1, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral EPI-7386 in Patients With Castration-Resistant Prostate Cancer
ClinicalTrials.gov Identifier: NCT04421222
Sponsor: ESSA Pharmaceuticals
Recruitment Contact: Karen Villaluna, 650-449-8400, kvillaluna@essapharma.com
Completion Date: April 2023
Image Credit: © Dr_Microbe [stock.adobe.com]
The first-in-class N-terminal domain androgen receptor inhibitor, EPI-7386, will be evaluated in combination with apalutamide (Erleada) or abiraterone acetate (Zytiga) plus prednisone in patients with prostate cancer in a phase 1 trial (NCT04421222), according to a clinical trial support agreement between ESSA Pharma Inc., and Janssen Research & Development, LLC.1
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. Previously, the FDA granted the agent a fast track designation for the treatment of adult male patients with metastatic castration-resistant prostate cancer (mCRPC) that is resistant to standard-of-care treatment.
The phase 1 clinical trial will evaluate the safety, pharmacokinetics, drug-drug interactions, and preliminary anti-tumor activity of EPI-7386 combined with either apalutamide or abiraterone acetate plus prednisone, under the terms of the agreement.
"We are pleased to have this agreement in place in order to further investigate EPI-7386 in combination with apalutamide and abiraterone acetate plus prednisone in a variety of prostate cancer patient populations," said David R. Parkinson, president and chief executive officer of ESSA Pharma, Inc., in a press release. "Preliminary clinical data from EPI-7386 combination studies with standard-of-care antiandrogens in [patients with] mCRPC have shown a favorable safety profile and encouraging early signs of anti-tumor activity.”
In cohort A of the phase 1 trial, investigators will look at the combination of EPI-7386 plus abiraterone acetate and prednisone in patients with mCRPC, as well as in patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Then, cohort B will be a Window of Opportunity study where patients with non-metastatic castration-resistant prostate cancer will receive up to 12 weeks of single agent EPI-7386, prior to adding standard-of-care apalutamide.2
Part 1a of the trial will evaluate the safety and tolerability of EPI-7386 in patients with prostate cancer. Part 1b will evaluate the 2 cohorts of patients with either mCRPC or mCSPC. For cohort A of this portion of the study, the safety and tolerability of EPI-7386 will be further evaluated in a patient population that has not been previously treated with chemotherapy, while in cohort B, investigators will assess the anti-tumor activity of EPI-7386 for up to 12 weeks prior to the start of standard of care therapy in patients with non-metastatic CRPC who were undisturbed by a prior second generation anti-androgen therapy or chemotherapy.
Patients will be administered a once daily oral dose of EPI-7386 between 200 mg and 1000 mg in cohorts 1-5 of the study. Cohorts 6-7 will administer EPI-7386 to patients as a twice daily oral dose of 800 mg or 1200 mg.
Inclusion criteria for part 1a includes having histologically, pathologically, or cytologically confirmed prostate cancer without small cell features, evidence of castration-resistant prostate cancer, presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI, limited available treatment options, and evidence of progressive disease. Additionally, patients must have recovered from toxicities related to any prior treatments, demonstrate adequate organ function, and have an ECOG performance status of 0-1 to be included in this part of the study. Patients included in part b cohort A have the same inclusion criteria as for part 1a, however, prior chemotherapy is not allowed for this cohort of patients.
Then for part 1b cohort B, patients with histologically, pathologically, or cytologically confirmed prostate cancer without small cell features with evidence of castration-resistant prostate cancer who received a first-generation anti-androgen as part of an initial combined androgen blockade therapy or as second-line hormonal therapy must show continuing disease progression off the anti-androgen for at least 4 weeks prior to enrollment were eligible for inclusion. At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors, estrogens, and any other anticancer therapy prior to enrollment, and at least 4 weeks must have elapsed from major surgery or radiation therapy prior to enrollment. Additionally, patients must have recovered from toxicities related to any prior treatments, have adequate organ function, and an ECOG performance status score of 0 to 1.
The primary end point for part 1a of the trial is the incidence of protocol-defined dose-limiting toxicities (DLT) during the DLT assessment period. For part 1b cohort A, the primary end pointis the proportion of patients with a decline from baseline in prostate specific antigen (PSA) blood concentrations of ≥50% and ≥90% at any time point during daily dosing with EPI-7386, and for part 1b cohort B, the primary end point is the proportion of patients with a decline from baseline in PSA blood concentrations of ≥50% and ≥90% at any time point during daily dosing with EPI-7386 up to week 12.
EPI-7386 is also being evaluated in a phase 1/2 clinical trial (NCT05075577) in combination with enzalutamide in patients with mCRPC who have not been treated with second-generation antiandrogen therapies. ESSA retains all rights to EPI-7386 worldwide.1
“We look forward to examining EPI-7386 with apalutamide and abiraterone acetate with prednisone in additional prostate cancer populations to assess the safety, tolerability, optimal dose[s] and preliminary anti-tumor activities of these approaches," added Parkinson, in the press release.
