ELACESTRANT in Women and Men with CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer: An Open-Label Multicenter Phase 2 Study (ELCIn)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stemline Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Jan 2024 → ongoing

Decision date (initial)

2023-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503214-68-00

WHO UTN

U1111-1290-2313

ClinicalTrials.gov

NCT05596409

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy of elacestrant in patients with ER+/HER2– advanced/metastatic breast cancer who received 1 or 2 prior hormonal therapy in the metastatic setting and no prior CDK4/6i

Secondary objectives 3

1. Evaluate other efficacy measures of elacestrant
2. Evaluate the quality of life of patients receiving elacestrant
3. Further characterize the safety of elacestrant

Conditions and MedDRA coding

metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient has signed the informed consent before all study-specific activities are conducted.
2. Women or men aged ≥18 years (or the minimum age of consent as per local law), at the time of informed consent signature. ● Female patients may be either postmenopausal or premenopausal/perimenopausal. o Postmenopausal status is defined by: - Age ≥60 years - Age <60 years and amenorrhea for 12 or more months (without an alternative cause) and follicle‑stimulating hormone (FSH) value and estradiol level within the local laboratory reference range for postmenopausal female patients. - Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy. ● Premenopausal or perimenopausal women and men must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 3 to 4 weeks before the start of trial therapy and is planning to continue LHRH during the study.
3. Documentation of histopathological or cytological confirmed ER+/HER2–breast cancer, per local laboratory, as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Note: In the context of this trial, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without PgR positivity.
4. At least 1 measurable lesion as per RECIST version 1.1 or a mainly lytic bone lesion for bone only disease.
5. ECOG performance status of 0 or 1.
6. Patient has adequate bone marrow and organ function, as defined by the following laboratory values: a. Absolute neutrophil count (ANC) ≥1.5 × 109/L b. Platelets ≥100 × 109/L c. Hemoglobin ≥9.0 g/dL d. Sodium, potassium, calcium (corrected for serum albumin), and magnesium, CTCAE v5.0 grade ≤1 e. Cockcroft-Gault based creatinine clearance ≥50 mL/min. Note: o Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) o Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) f. Serum albumin ≥3.0 g/dL (≥30 g/L) g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN) in the absence of liver metastasis. h. If the patient has liver metastases, ALT, and AST ≤5.0 × ULN i. Total serum bilirubin <1.5 × ULN except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN. Note: Laboratory assessments may be repeated once during the Screening Phase after supplementation or transfusions. (a single red blood cells transfusion is allowed once during the screening period).
7. The patient is able and willing to comply with study protocol requirements.
8. Patient has received at least 1 (and up to 2) prior hormonal therapy in the advanced/metastatic setting.
9. Radiological disease progression during or after the most recent therapy in the advanced/metastatic setting.
10. Patients with disease relapse while on adjuvant endocrine therapy after the 2 first years, or with disease relapse within 12 months of completing adjuvant endocrine therapy are allowed (i.e., patients with secondary-resistant breast cancer according to the 5th ESO-ESMO international consensus guidelines for advanced breast cancer, Cardoso et al 2020). This therapy will be considered as first line treatment for eligibility purposes.

Exclusion criteria 14

1. Active or newly diagnosed central nervous system (CNS) metastases, including meningeal carcinomatosis. Note: Patients with stable brain metastases are allowed, only if the patient has completed local therapy and is on a stable or decreasing dose of corticosteroids (≤ 2.0 mg/day of dexamethasone or equivalent) for at least 4 weeks before starting treatment in this study. In addition, any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
2. Men who do not agree to abstain from donating/freezing sperm, or to use a highly effective method of contraception within 28 days of the first dose of study treatment through 120 days after the last dose of study treatment. For subjects (who have not undergone vasectomy) with female partners of childbearing potential, the subject and his partner must use highly effective methods of contraception, as described in Appendix E.
3. Females who are pregnant or breastfeeding. Females should not get pregnant during study treatment and for 120 days after last dose of study treatment. Females should not breastfeed during administration of elacestrant and for 1 week after receiving the last dose.
4. Patient is currently receiving or received any of the following medications prior to first dose of trial therapy: o Any anti-cancer therapy within 14 days (28 days in case of anticancer antibody-based treatments) or 5 half-lives, whichever is shorter. o Fulvestrant treatment (last injection) <42 days before first dose of study drug o Any other endocrine therapy <14 days or 5 half-lives, whichever is shorter, before first dose of study drug o Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter, (Refer to Section 5.7.3), o Herbal preparations/medications within 7 days. These include, but are not limited to, St. John’s wort, kava, ephedra (ma huang), ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng
5. Any severe medical or psychiatric condition that in the opinion of the investigator(s) would preclude the patient’s participation in a clinical study.
6. Patients with visceral crisis who are at risk of life-threatening complications in the short term, including but not limited to: massive uncontrolled effusions (peritoneal, pleural, pericardial) and liver involvement of >50%.
7. Prior treatment with chemotherapy, CDK4/6i (including adjuvant), elacestrant, other investigational selective estrogen receptor degraders (SERDs) or alike agents such as selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCANs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), in the advanced/metastatic setting.
8. Patient has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative treatment.
9. Uncontrolled significant active infections. ● Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening. ● Patients known to be HIV+ are allowed if they have undetectable viral load at baseline.
10. Major surgery within 28 days before starting trial therapy.
11. Systemic radiotherapy within 14 days before starting trial therapy, or central nervous system radiotherapy within 28 days before starting trial therapy. Inability to take oral medication, refractory or chronic nausea, gastrointestinal condition (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that may impact the absorption of study drug.
12. Known intolerance to elacestrant or any of its excipients (see Table 7).
13. Females of childbearing potential who do not agree to use a highly effective non-hormonal method of contraception and to abstain from donating/freezing ova within 28 days of the first dose of study treatment through 120 days after the last dose of study treatment. Highly effective non-hormonal methods of contraception are described in Appendix E.
14. Patients with only disease relapse while on the first 2 years of adjuvant endocrine therapy i.e., patients with primary endocrine resistance, are not eligible.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS), as per investigator’s assessment (PFS defined as time from the date of the first dose to the date of the first radiological documentation of disease progression or death, whichever comes first)

Secondary endpoints 4

1. Objective Response Rate (ORR): proportion of patients who achieve a best overall response (BOR) of partial response (PR) or complete response (CR)
2. Duration of Response (DoR): time from the date of first documented CR/PR until the first radiological documentation of disease progression or death, whichever comes first
3. Clinical Benefit Rate (CBR): proportion of patients who achieve a BOR of confirmed CR/PR or durable stable disease (duration at least 24 weeks from date of first dose)
4. Overall Survival (OS): time from the date of the first dose to the date of death from any cause

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stemline Therapeutics Inc.

Sponsor organisation

Stemline Therapeutics Inc.

Address

750 Lexington Avenue

City

New York

Postcode

10022-1200

Country

United States

Scientific contact point

Organisation

Stemline Therapeutics Inc.

Contact name

Carlos A. Garay

Public contact point

Organisation

Stemline Therapeutics Inc.

Contact name

Carlos A. Garay

Third parties 5

Locations

2 EU/EEA countries · 5 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