Study of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-site, global, open label study which includes a Phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with with or without brain metastases from ER positive, HER-2 negative breast cancer. Phase 1b is designed to select the recommended phase 2 dose and will be followed by a randomized Phase 2 evaluation of elacestrant alone or in combination with abemaciclib in women and men with brain metastases from ER positive, HER-2 negative breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stemline Therapeutics, Inc.

Criteria

Inclusion Criteria:

• 1. Patient has the signed informed consent form before any study-related activities according to local guidelines.

2. Women or men aged ≥18 years, at the time of informed consent signature.

• Female patients may be either postmenopausal or premenopausal or perimenopausal. Postmenopausal status is defined by:

1. Age ≥60 years

2. Age <60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value <40 pg/mL (140 pmol/L) or in postmenopausal ranges per local reference ranges

3. Documentation of prior surgical sterilization (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, at least 1 month before first dose of trial therapy).

• Premenopausal or perimenopausal women must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planning to continue LHRH during the study.

• For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/ml.

3. Patient must have ER positive, HER-2 negative tumor status as confirmed by local laboratory testing either from a fresh biopsy or from an archival tissue obtained no more than 2 years prior to signing of the informed consent form. For Phase 1b, the presence of brain metastases is allowed but not required for eligibility, in this case, at least 1 measurable lesion outside the brain is required.

• ER and HER 2 testing must be performed in the following manner:

• Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry (IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology (ASCO) recommendations for ER testing, with or without progesterone receptor (PGR) positivity

• HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane protein expression or an in situ hybridization negative result as defined in the 2013 or 2018 ASCO recommendations for HER 2 testing 4. In Phase 2, patients must have at least one active and measurable brain metastasis per RECIST version 1.1

• Any of the following qualifies brain metastases as active:

1. Newly diagnosed brain metastasis in patients who never received prior CNS-directed therapy.

2. Newly diagnosed brain metastasis outside any area that was previously subjected to CNS-directed therapy

3. Brain metastases that are progressing in an area that has previously been subjected to CNS-directed therapy

• For lesions, including brain metastases, to qualify as measurable, and possibly be selected as target lesions, per RECIST version 1.1 (Appendix C), the longest diameter must be ≥10 mm by CT or magnetic resonance imaging (MRI).

5. Patients must be off corticosteroids or receiving a stable or decreasing corticosteroid dose at the time of starting trial therapy. The dose must be ≤2.0 mg/day of dexamethasone or equivalent.

6. Any neurological symptoms of brain metastases must be stable for at least 4 weeks before starting trial therapy.

7. Patient has received prior therapy in the metastatic setting including:

• At least one endocrine therapy

• Up to two chemotherapy regimens

• Up to two prior CDK 4/6 inhibitors, not including abemaciclib

• If recurrence was observed while on adjuvant therapy or within 12 months of end of adjuvant therapy, this therapy will be counted as part of required prior therapy for eligibility.

• Toxicity from prior therapy must be resolved to National Cancer Institute (NCI) CTCAE version 5.0 Grade ≤1, with the exception of alopecia and peripheral sensory neuropathy (Grade ≤2).

8. Patient has documented intra- and/or extra-cranial radiological progression or recurrence while on or after the most recent therapy.

9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

10. Patient has adequate bone marrow and organ function, as defined by the following laboratory values (in the absence of transfusion of red blood cells or platelets or the use of growth factors within the preceding 4 weeks):

1. Absolute neutrophil count (ANC) ≥1.5 × 109/L

2. Platelets ≥100 × 109/L

3. Hemoglobin ≥9.0 g/dL

4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE Grade ≤1 (if screening assessments are abnormal, these assessments may be repeated up to 2 times; subjects may receive appropriate supplementation or treatment prior to reassessment)

5. Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL/min

6. Serum albumin ≥3.0 g/dL (≥30 g/L)

7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN. If the patient has liver metastases, ALT and AST ≤5 × ULN

8. 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 11. The patient is able and willing to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Immediate CNS-specific treatment is likely to be required, per the treating physician's assessment.

2. Patient has leptomeningeal metastases, defined as having positive CSF cytology or unequivocal radiologic or clinical evidence of leptomeningeal involvement.

3. Breast cancer treatment-naïve patients in the metastatic setting. Patients who experience a recurrence while on adjuvant therapy or within 12 months of end of adjuvant therapy are allowed.

4. Prior therapy with elacestrant or abemaciclib in the metastatic setting. Note:

Use of abemaciclib in the adjuvant setting is allowed if the last treatment administration was more than 12 months prior to first recurrence.

5. Patient has a concurrent malignancy or malignancy within 3 years of enrollment, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer).

6. Currently participating in another breast cancer intervention clinical study. Patients who are being followed for overall survival for another clinical trial with no therapy and study intervention are allowed.

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

• Fulvestrant treatment (last injection) <42 days before first dose of study drug

• Any other endocrine therapy <14 days before first dose of study drug

• Chemotherapy or other anti-cancer therapy <21 days before first dose of study drug

• Any investigational anti-cancer drug therapy within <28 days or <5 half lives, whichever is shorter

• Bisphosphonates or RANKL inhibitors initiated or dose changed <3 months prior to first dose of study drug.

8. Radiation therapy (other than CNS directed) within 14 days before the first dose of study drug.

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 as long as they have undetectable viral load at baseline.

10. Major surgery within 4 weeks of starting trial therapy. 11. Inability to take oral medication, or presence of malabsorption syndrome or any other uncontrolled gastrointestinal condition.

12. Females of childbearing potential who:

• Within 28 days of study entry, did not use a highly effective method of contraception, which includes any of the following:

1. Intrauterine device

2. Double-barrier contraception

3. Total abstinence

4. Have a vasectomized partner with confirmed azoospermia. • Do not agree to use a highly effective method of contraception, as described above, throughout the entire study period and for 28 days after trial therapy discontinuation.

13. Men who do not agree abstain from donating sperm or to use a highly effective method of contraception during the treatment period and for 120 days thereafter. Highly effective methods include any of the following:

a. Double-barrier contraception b. Total abstinence c. Vasectomized with confirmed azoospermia. d. Female partner with intrauterine device. 14. Females who are breastfeeding or pregnant. 15. Known intolerance to either study drug or any of the excipients. 16. Patients currently receiving or received any of the following medications prior to first dose of trial therapy:

a. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 21 days prior to initiating trial therapy b. Herbal preparations/medications These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng within 21 days prior to initiating trial therapy c. Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization.

17. Any medical or other condition that in the opinion of the investigator(s) would preclude the patient's participation in a clinical study.

18. Evidence of ongoing alcohol or drug abuse