An Open-label Multicenter Phase 1b-2 Study of Elacestrant in Combination With Abemaciclib in Women and Men With Brain Metastasis From Estrogen Receptor Positive, HER-2 Negative Breast Cancer

Plain English Summary

Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+/HER-2- Breast Cancer is a Phase 2 clinical trial sponsored by Stemline Therapeutics, Inc. studying Breast Neoplasms, Brain Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Central Nervous System Neoplasms, Brain Diseases, Central Nervous System Diseases. This study is testing a combination of two drugs, elacestrant and abemaciclib, to see how effective they are in treating advanced breast cancer that has spread to the brain. It is for women and men with estrogen receptor-positive (ER+), HER-2 negative breast cancer that has spread to the brain. Participants will receive the study drugs and will be monitored closely for side effects and how well the treatment works. This is an open-label study, meaning both the participants and the researchers will know which treatments are being given. There are no direct alternatives offered within this trial, but standard treatments for brain metastases from breast cancer include radiation therapy, surgery, and other systemic therapies. The trial aims to enroll 73 participants.

Official Summary

This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain metastases from estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2) negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose (RP2D) and is followed by an ongoing phase 2 evaluation of elacestrant in combination with abemaciclib in participants with active brain metastases from ER-positive, HER-2 negative breast cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Men and women aged 18 and older can join. Participants must have ER-positive, HER-2 negative breast cancer that has spread to the brain and is measurable. Women who are pre- or perimenopausal and men must be receiving a specific hormone therapy (LHRH agonist). Postmenopausal women also qualify. Participants should have had no more than one seizure in the last 4 weeks and be on a stable or decreasing dose of corticosteroids if they are taking them. This trial is studying Breast Neoplasms, Brain Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Central Nervous System Neoplasms, Brain Diseases, Central Nervous System Diseases, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the combination therapy shrinks tumors in the brain and body, indicating its effectiveness in controlling the cancer. The specific primary outcome measures are: Phase 1b: RP2D (Cycle 1 (28 days)); Phase 2: Objective Response Rate (ORR) Per Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) (3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for effective treatments for patients with ER+/HER-2- breast cancer that has spread to the brain, a common and challenging complication. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Neoplasms, Brain Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Central Nervous System Neoplasms, Brain Diseases, Central Nervous System Diseases, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in a large patient population, with potential for improved outcomes if the combination therapy proves effective, signaling a promising investment opportunit Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of elacestrant and abemaciclib, and how this trial fits with other treatment options. Be prepared for regular clinic visits for drug administration, blood tests, and imaging scans to monitor your response and any side effects. Understand that this is an open-label study, meaning you and your doctor will know which treatments you are receiving. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 73 participants

Interventions

• DRUG: Elacestrant — 300 mg, 400 mg
• DRUG: Abemaciclib — 100 mg, 150 mg

Primary Outcomes

• Phase 1b: RP2D (Cycle 1 (28 days))
• Phase 2: Objective Response Rate (ORR) Per Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) (3 years)

Secondary Outcomes

• Phase 1b and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (3 years)
• Phase 1b and 2: Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) (Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days))
• Phase 1b and 2: Maximum Observed Plasma Concentration (Cmax) (Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days))
• Phase 1b and 2: Time to Reach Cmax (Tmax) (Cycle 1 Day 15 (predose and up to 24 hours postdose) (Cycle length = 28 days))
• Phase 1b: ORR As Per Local Investigator's Assessment and Per BICR (3 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Participant 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 participants may be either postmenopausal or pre/perimenopausal. Postmenopausal status is defined by:

     1. Age ≥60 years
     2. Age \<60 years and amenorrhea for 12 or more months without an alternative cause) and follicle stimulating hormone and estradiol in postmenopausal ranges per local reference ranges
     3. Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy).
   * Pre-menopausal / peri-menopausal women and men must be concurrently receiving a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 3-4 weeks before the start of trial therapy and is planning to continue LHRH during the study.
3. Participant must have ER-positive, HER-2 negative tumor status as confirmed by local laboratory testing 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, participants 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 participants who never received prior central nervous system (CNS)-directed therapy.
     2. Newly diagnosed brain metastasis outside any area that was previously subjected to CNS-directed therapy.
     3. Brain metastases demonstrating unequivocal progression in the opinion of the treating investigator 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, the longest diameter must be ≥10 millimeters \[mm\] by computed tomography \[CT\] or magnetic resonance imaging \[MRI\]).
   * In 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.
5. Participants receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 7 days prior to baseline and not receiving doses higher than 4 mg of dexamethasone per day or equivalent.
6. Participants have experienced no more than one seizure within 4 weeks prior to starting trial therapy.
7. Participants' prior therapy received in the metastatic setting includes:

   * At least one endocrine therapy
   * Up to two chemotherapy regimens
   * Up to two lines of prior cyclin-dependent kinase (CDK) 4/6 inhibitor, not including abemaciclib

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

   Note 2: Chemotherapy refers to not targeted cytotoxic agents (for example, alkylating agents, taxanes, nucleotide analogs, platinum-based drugs, vinca alkaloids, etc) and antibody drug conjugates (ADCs). Targeted therapies (for example, kinase inhibitors) are not considered chemotherapy for eligibility purposes. Not targeted cytotoxic agents administered for less than 1 cycle will not be counted as a prior chemotherapy regimen.
8. Participant has documented intracranial and/or extracranial radiological progression or recurrence while on or after the most recent therapy.
9. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
10. Participant has a life expectancy ≥ 12 weeks.
11. Participant has adequate bone marrow and organ function, as defined by the following laboratory values:

    1. Absolute neutrophil count (ANC) ≥1.5 × 10\^9/liter (L)
    2. Platelets ≥100 × 10\^9/L
    3. Hemoglobin ≥9.0 grams (g)/deciliter (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; participants may receive appropriate supplementation or treatment prior to reassessment)
    5. Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL/minute
    6. Serum albumin ≥3.0 g/dL (≥30 g/L)
    7. Liver function tests:

       In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN). If the participant has liver metastases, ALT and AST ≤5.0 × ULN.
    8. Total serum bilirubin \<1.5 × ULN except for participants with Gilbert's syndrome who may be included if the total serum bilirubin 

Trial Locations

• Providence Medical Foundation, Fullerton, California, United States
• California Research Institute, Los Angeles, California, United States
• Carle Cancer Center, Urbana, Illinois, United States
• Dana-Farber Cancer Institute, Boston, Massachusetts, United States
• Henry Ford Hospital, Detroit, Michigan, United States
• Miami Valley Hospital South, Centerville, Ohio, United States
• Oregon Health & Science University, Portland, Oregon, United States
• SCRI Oncology Partners, Nashville, Tennessee, United States
• University of Texas MD Anderson Cancer Center, Houston, Texas, United States
• UT Health San Antonio University of Texas, San Antonio, Texas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• ER-Positive Breast Cancer
• HER-2 Negative Breast Cancer
• Brain Metastases
• Estrogen Receptor Positive Neoplasms
• HER-2 Negative Neoplasms
• Neoplasms of the Central Nervous System
• Oncology
• Endocrine Therapy Resistance

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