VOSILASARM for Breast cancer | Hormone receptor positive HER2-negative breast cancer | Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- 1. Women 18 years or older at the time of informed consent\n- 2. Histologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced breast adenocarcinoma as defined by the 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. Patients enrolled into the combination arms of Module B must be assessed by the investigator to qualify for treatment with the combination agent(s) as standard-of-care.\n- 3. Biopsy-proven AR+ HER2- and ER+ breast cancer on a fresh biopsy from a primary tumour or metastatic tumour lesion. Where a fresh biopsy is not feasible, an archival tumour sample (formalin-fixed, paraffin embedded block(s) or slides can be used for this purpose providing they are not more than 10 years old. Hormonal analysis of cytology specimens e.g. malignant pleural effusion may be used to confirm receptor status. Retrospective confirmatory testing is allowed. 3.1 AR+ breast cancer is defined as ___ AR nuclei staining by IHC either locally by a CLIA-certified laboratory or centrally. The test should be performed in accordance with clinical guidelines delineated by ASCO, CAP and NCCN 3.2 HER2- breast cancer, defined as negative by immunohistochemistry (IHC) score of 0 or 1+. If IHC is equivocal at 2+, a negative in situ hybridisation (ISH) test (HER2/CEP17 ratio of <2.0) is required\n- 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1\n- 5. Postmenopausal, based on protocol-defined criteria on page 56\n- 6. Module A: Received ___ prior lines of endocrine therapy in advanced/metastatic setting, which may have included both an AI (alone or in combination) and SERD (alone or in combination); at least one must have been given in combination with a CDK 4/6 inhibitor. Module B: Patients must be a candidate for the combination agent(s) as standard-of-care treatment.\n- 7. Received ___ of chemotherapy in the advanced/metastatic setting.\n- 8. Endocrine-therapy–sensitive breast cancer, defined as: a) greater than 2 years of adjuvant endocrine therapy prior to the development of advanced or metastatic disease, OR b) previous response (without disease progression for at least 6 months) to one of the following treatments in the advanced/metastatic setting: SERD +/- CDK 4/6 inhibitor, AI +/- CDK 4/6 inhibitor\n- 9. Measurable disease, defined by Response Evaluation in Solid Tumours (RECIST) v1.1, or bone-only evaluable disease (e.g., with a blastic or lytic component that can be imaged)\n- 10. Estimated life expectancy >3 months\n- 11. In the opinion of the Investigator, all other relevant medical conditions must be well-managed and stable for at least 28 days prior to first administration of study drug\n- 12. Adequate haematological and organ function, based on protocol-defined criteria on page 57\n- 13. Left ventricular ejection fraction >50% (by echocardiogram or multi-gated acquisition [MUGA] scan)\n- 14. Willing and able to participate in all required evaluations and procedures in this study protocol\n- 15. Ability to understand and provide written informed consent before any study-specific procedures, sampling, or analyses, including access to archival tumour tissue\n- 16. Combination Agents (Module B): All combination agents are established standard-of-care therapies and will be prescribed in accordance with their respective labels, local clinical practice and protocol inclusion-exclusion criteria. As such, any specific warnings, precautions and contraindications must be considered in addition to the inclusion-exclusion criteria."}

Exclusion criteria

• {"criterion_text":"- 1. Prior anti-cancer or investigational drug treatment, within protocol-defined time windows on page 58\n- 2. Prior treatment with Enobosarm\n- 3. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens\n- 4. Radiation therapy within 14 days prior to the first dose of study drug. Short courses of palliative radiation therapy during the study might be allowed following discussion with and approval by the Medical Monitor.\n- 5. 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\n- 6. Symptomatic cerebral metastases or central nervous system (CNS) involvement, based on protocol-defined criteria on page 59\n- 7. Confirmed 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\n- 8. 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\n- 9. 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\n- 10. Congestive heart failure Grades III–IV according to the New York Heart Association at the time of screening\n- 11. Myocardial infarction or unstable angina within the previous 6 months\n- 12. Any other concurrent severe and/or uncontrolled medical or surgical condition which, in the view of the Investigator, could compromise the patient’s participation in the study\n- 13. Active infection requiring intravenous or oral antibiotics within 14 days before the first dose of study drug\n- 14. Any major surgical procedure (planned or anticipated, in the Investigator’s judgement) within 14 days of the first dose of study drug\n- 15. Known contraindications or hypersensitivity to SARMs or the excipients of the study drug\n- 16. Known contraindications or hypersensitivity to combination agents or their excipients\n- 17. Module B: Prior treatment with: –Arm 1: Standard treatment 1 –Arm 2: Standard treatment 2 –Arm 3: Standard treatment 3\n- 18. Received a live vaccine within 28 days prior to planned enrolment; combination module B-Arm 2 only\n- 19. A history of (non-infectious) pneumonitis requiring steroids, or current pneumonitis; combination module B-Arm 2 only\n- 20. The patient is unable to swallow___ and/or has a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis\n- 21. Any other condition that would, in the Investigator’s judgement, contraindicate the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures\n- 22. 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\n- 23. Known active hepatitis B or C\n- 24. Patients with active human immunodeficiency virus (HIV) infection. Patients living with HIV are eligible if they have CD4+ T-cell count ≥ 350 cells/µL, no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the past 12 months, and can be managed on a regimen consistent with this protocol’s permitted concomitant medications"}

Primary endpoints

• {"endpoint_text":"- 1. Module A: Incidence of dose-limiting toxicities (DLTs) during Cycle 1 of EP0062 treatment (28 days)","definition_or_measurement_approach":"DLTs assessed during Cycle 1 (28 days) of EP0062 treatment"}
• {"endpoint_text":"- 2. Module A: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)","definition_or_measurement_approach":"Incidence and severity as reported in study safety assessments (no further detail provided in summary)"}
• {"endpoint_text":"- 3. Module A: Optimal monotherapy dose and a clinical dose for evaluation in the combination arms of Module B","definition_or_measurement_approach":"Determination of optimal clinical monotherapy dose through Module A dose-finding/optimization (no specific algorithm provided in summary)"}
• {"endpoint_text":"- 4. Module B: Incidence and severity of AEs and SAEs","definition_or_measurement_approach":"Incidence and severity as reported in study safety assessments (no further detail provided in summary)"}
• {"endpoint_text":"- 5. Module B: Recommended clinical dose(s) for combination therapy","definition_or_measurement_approach":"Recommendation based on Module B evaluation (no additional measurement details provided in summary)"}

Secondary endpoints

• {"endpoint_text":"- 1. Module A: Plasma PK parameters AUC0–48, AUClast, AUCinf, Cmax and/or Cmin, tmax, t½, CL/F, V/F, and/or Vz/F","definition_or_measurement_approach":"Plasma pharmacokinetic parameters as listed (AUC0–48, AUClast, AUCinf, Cmax/Cmin, tmax, t½, CL/F, V/F, Vz/F)"}
• {"endpoint_text":"- 2. Module A: Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. Module A: Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4. Module A: Progression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 5. Module A: Clinical benefit rate (CBR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. Module A: Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 7. Module A: PD response to EP0062","definition_or_measurement_approach":""}
• {"endpoint_text":"- 8. Module B: Plasma PK parameters of EP0062 AUC0–24, AUClast, AUCinf, Cmax and/or Cmin, tmax, t½, CL/F, V/F, and/or Vz/F","definition_or_measurement_approach":"Plasma pharmacokinetic parameters as listed (AUC0–24, AUClast, AUCinf, Cmax/Cmin, tmax, t½, CL/F, V/F, Vz/F)"}
• {"endpoint_text":"- 9. Module B: ORR","definition_or_measurement_approach":""}
• {"endpoint_text":"- 10. Module B: DOR","definition_or_measurement_approach":""}
• {"endpoint_text":"- 11. Module B: PFS","definition_or_measurement_approach":""}
• {"endpoint_text":"- 12. Module B: CBR","definition_or_measurement_approach":""}
• {"endpoint_text":"- 13. Module B: OS","definition_or_measurement_approach":""}

Spain

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

02-10-2025

Processing Time Days

661

Number Of Sites

4

Number Of Participants

25

Primary sponsor

Full Name

Ellipses Pharma Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Median Technologies

Responsibilities

Central Imaging

Name

Icon Clinical Research LLC

Responsibilities

code 4

Name

Discovery Life Sciences Biomarker Services GmbH

Responsibilities

Biomarkers; code 4

Name

Theradex (Europe) Limited

Responsibilities

codes: 1,10,11,12,3,5,6,7,8

Name

Medrio Inc.

Responsibilities

code 4

Name

Fisher Clinical Services GmbH

Responsibilities

code 14

Name

Distefar Del Sur S.L.

Responsibilities

code 14

Third parties

• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"Biomarkers; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Distefar Del Sur S.L.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Theradex (Europe) Limited","duties_or_roles":"codes: 1,10,11,12,3,5,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}