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 as monotherapy and in combination in Patients with Relapsed Locally Advanced or Metastatic AR+/HER2-/ER+ Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ellipses Pharma Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Mar 2024 → ongoing

Decision date (initial)

2024-01-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ellipses Pharma Ltd.

External identifiers

EU CT number

2023-507738-26-00

ClinicalTrials.gov

NCT05573126

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Dose response

Module A
- Evaluate the safety and tolerability of EP0062
- Determine the optimal clinical dose(s) of the new formulation of EP0062 given as monotherapy and identify a dose for evaluation in the combination arms of Module B

Module B
- Evaluate the safety and tolerability of EP0062 in combination therapy

Secondary objectives 5

1. Module A: Characterise the PK profile of EP0062
2. Module A: Evaluate the preliminary efficacy of EP0062
3. Module A: Evaluate the PD response to EP0062
4. Module B: Characterise the PK profile of EP0062 in combination therapy
5. Module B: Evaluate the preliminary efficacy of EP0062 in combination therapy

Conditions and MedDRA coding

Breast Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Women 18 years or older at the time of informed consent
2. 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)
3. 10. Estimated life expectancy >3 months
4. 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
5. 12. Adequate haematological and organ function, based on protocol-defined criteria on page 57
6. 13. Left ventricular ejection fraction >50% (by echocardiogram or multi-gated acquisition [MUGA] scan)
7. 14. Willing and able to participate in all required evaluations and procedures in this study protocol
8. 15. Ability to understand and provide written informed consent before any study-specific procedures, sampling, or analyses, including access to archival tumour tissue
9. 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.
10. 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.
11. 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
12. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
13. 5. Postmenopausal, based on protocol-defined criteria on page 56
14. 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.
15. 7. Received ___ of chemotherapy in the advanced/metastatic setting.
16. 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

Exclusion criteria 24

1. 1. Prior anti-cancer or investigational drug treatment, within protocol-defined time windows on page 58
2. 10. Congestive heart failure Grades III–IV according to the New York Heart Association at the time of screening
3. 11. Myocardial infarction or unstable angina within the previous 6 months
4. 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
5. 13. Active infection requiring intravenous or oral antibiotics within 14 days before the first dose of study drug
6. 14. Any major surgical procedure (planned or anticipated, in the Investigator’s judgement) within 14 days of the first dose of study drug
7. 15. Known contraindications or hypersensitivity to SARMs or the excipients of the study drug
8. 16. Known contraindications or hypersensitivity to combination agents or their excipients
9. 17. Module B: Prior treatment with: –Arm 1: Standard treatment 1 –Arm 2: Standard treatment 2 –Arm 3: Standard treatment 3
10. 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
11. 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
12. 2. Prior treatment with Enobosarm
13. 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
14. 23. Known active hepatitis B or C
15. 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
16. 3. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens
17. 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.
18. 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
19. 6. Symptomatic cerebral metastases or central nervous system (CNS) involvement, based on protocol-defined criteria on page 59
20. 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
21. 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
22. 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
23. 18. Received a live vaccine within 28 days prior to planned enrolment; combination module B-Arm 2 only
24. 19. A history of (non-infectious) pneumonitis requiring steroids, or current pneumonitis; combination module B-Arm 2 only

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. 1. Module A: Incidence of dose-limiting toxicities (DLTs) during Cycle 1 of EP0062 treatment (28 days)
2. 2. Module A: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
3. 3. Module A: Optimal monotherapy dose and a clinical dose for evaluation in the combination arms of Module B
4. 4. Module B: Incidence and severity of AEs and SAEs
5. 5. Module B: Recommended clinical dose(s) for combination therapy

Secondary endpoints 13

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ellipses Pharma Limited

Sponsor organisation

Ellipses Pharma Limited

Address

10 Stratton Street

City

London

Postcode

W1J 8LG

Country

United Kingdom

Scientific contact point

Organisation

Ellipses Pharma Limited

Contact name

Tobi Arkenau

Public contact point

Organisation

Ellipses Pharma Limited

Contact name

Arturo Maldonado

Third parties 7

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications