Phase 1/2 Study to Evaluate EP0062 in Patients With Relapsed Locally Advanced or Metastatic Androgen Receptor Positive (AR+)/HER2-/ER+ Breast Cancer

• ClinicalTrials.gov Identifier: NCT05573126
• Recruitment Status: Not yet recruiting
• First Posted: October 10, 2022
• Last Update Posted: October 10, 2022
• Sponsor: Ellipses Pharma
• Information provided by (Responsible Party): Ellipses Pharma

Tracking Information

• First Submitted Date: October 3, 2022
• First Posted Date: October 10, 2022
• Last Update Posted Date: October 10, 2022
• Estimated Study Start Date: December 2022
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2022)

• Incidence of dose-limiting toxicities (DLTs) during Cycle 1 of EP0062 treatment [ Time Frame: first 28 days ]
  Module A
• Maximum tolerated dose (MTD) and doses for evaluation in the expansion cohorts [ Time Frame: 1 year ]
  Module A
• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: up to 30 days after the end of treatment ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 5, 2022)

• Plasma pharmacokinetic (PK) parameters - Half life [ Time Frame: 1, 2, 4, 8, 24 and 48 hours during cycle 1 ]
• Plasma pharmacokinetic (PK) parameters - Cmax [ Time Frame: 1, 2, 4, 8, 24 and 48 hours during cycle 1 ]
• Plasma pharmacokinetic (PK) parameters - Area under the curve (exposure) [ Time Frame: 1, 2, 4, 8, 24 and 48 hours during cycle 1 ]
• Tumour response [ Time Frame: screening and every 8 weeks up to 12 months ]
• Clinical Benefit Rate (CBR) [ Time Frame: every 8 weeks up to 12 months ]
• Objective Response Rate (ORR) [ Time Frame: every 8 weeks up to 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1/2 Study to Evaluate EP0062 in Patients With Relapsed Locally Advanced or Metastatic Androgen Receptor Positive (AR+)/HER2-/ER+ Breast Cancer
• Official Title: A Modular, Open-Label, Multi-Centre Phase 1/2 Dose-Finding, Optimisation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0062 in Patients With Relapsed Locally Advanced or Metastatic AR+/HER2-/ER+ Breast Cancer
• Brief Summary: The aim of this study is to identify the optimal dose for EP0062 as monotherapy and to assess its Safety, Tolerability, Pharmacokinetics, and Efficacy in Patients with Relapsed Locally Advanced or Metastatic AR+/HER2-/ER+ Breast Cancer
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hormone Receptor-positive Breast Cancer
• Hormone Receptor Positive HER-2 Negative Breast Cancer
• Metastatic Breast Cancer

Intervention

Drug: EP0062

EP0062 is an orally administered investigational selective androgen receptor modulator (SARM)

Study Arms

• Experimental: Module B - EP0062 Dose level 1
  Patients randomised to one of the 2 expansion doses selected from Module A, with up to 30 patients included per dose level, to further characterise the safety and efficacy of EP0062.
  Intervention: Drug: EP0062
• Experimental: Module B - EP0062 Dose level 2
  Patients randomised to one of the 2 expansion doses selected from Module A, with up to 30 patients included per dose level, to further characterise the safety and efficacy of EP0062.
  Intervention: Drug: EP0062

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 5, 2022): 128
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Women 18 years or older at the time of informed consent
2. Histologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced breast adenocarcinoma as defined by the American Joint Committee on Cancer/Union for International Cancer Control/Tumour Node Metastases (AJCC/UICC TNM) staging classification (8th Ed, 2017) and where no conventional therapy is available or considered appropriate by the Investigator or is declined by the patient
3. Availability of archival tumour sample (formalin-fixed, paraffin-embedded block(s) or slides from a primary tumour or biopsy of a metastatic tumour lesion or lesions); in the absence of an archival tumour sample, or if only archival bone tissue is available, a fresh biopsy will need to be collected

4. Biopsy-proven AR+ and ER+ breast cancer

   • For Module A, AR+ breast cancer is defined as ≥ 10% AR nuclei staining by central immunohistochemistry (IHC) using the Ventana assay
   • For Modules B and C, AR+ breast cancer is defined as ≥ 30% AR nuclei staining by central IHC using the Ventana assay
5. HER2-negative breast cancer, defined as negative by fluorescence in situ hybridisation (FISH) or IHC score of 0 or 1+. If IHC is equivocal at 2+, a negative FISH test (HER2/Amplification of the centromeric region of chromosome 17)CEP17 ratio of <2.0) is required

6. Postmenopausal, as defined by at least one of the following:

   1. Age over 60 years
   2. Amenorrhea > 12 months at the time of informed consent and an intact uterus, with follicle-stimulating hormone (FSH) and oestradiol in the postmenopausal ranges (as per local practice)
   3. FSH and oestradiol in the postmenopausal ranges (as per local practice) in women aged <55 years who have undergone hysterectomy
   4. Prior bilateral oophorectomy

Exclusion Criteria:

Patients with any of the following will not be included in the study:

1. Prior anti-cancer or investigational drug treatment within the following time windows:

   • Any chemotherapy within 21 days prior to the first dose of study drug
   • Any non-chemotherapy investigational anti-cancer drug < 5 half-lives (28 days for biologics) or < 14 days for small-molecule therapeutics or if half-life is not known
   • Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug
   • Fulvestrant or other investigational Selective Estrogen Receptor Degraders (SERDs) within 21 days prior to first dose of study drug
2. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens
3. Radiation therapy within 14 days prior to the first dose of study drug and scheduled to have radiation therapy during participation in this study. Short courses of palliative radiation therapy during the study might be allowed following discussion with and approval by the Medical Monitor. Palliative radiotherapy within 6 weeks prior to first dose of study drug is permitted
4. Unresolved or unstable serious toxic side effects of prior chemotherapy or radiotherapy, i.e., ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except fatigue, alopecia, and Grade 2 chemotherapy-induced neuropathy
5. Confirmed Corrected QT Interval by Fridericia (QTcF) > 470 ms on screening ECG, or history of torsades de pointes (TdP), or history of congenital long QT syndrome, or immediate family history of long QT syndrome, unexplained sudden death at a young age, or sudden cardiac death
6. Any other clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third-degree heart block); rate-controlled atrial fibrillation is permitted
7. Concomitant medications that prolong the corrected QT interval and/or increase the risk for TdP that cannot be discontinued or substituted with another drug within 5 half-lives or 14 days before the first dose of study drug, whichever is longer
8. Congestive heart failure Grades II-IV according to the New York Heart Association at the time of screening
9. Myocardial infarction or unstable angina within the previous 6 months
10. Patients receiving medications that are known to be strong inhibitors or inducers of CYP3A4 within 5 half-lives or 14 days, whichever is longer, before the first dose of study drug

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Andrew Mazur; +44 (0)20 3743 0992; andrew@ellipses.life

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05573126
• Other Study ID Numbers: EP0062-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ellipses Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Ellipses Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ellipses Pharma
• Verification Date: October 2022