The goal of this study is to evaluate the safety and efficacy of elacestrant in combination with trastuzumab deruxtecan (T-DXd) in participants with hormone receptor-positive (HR+), HER2-low or HER2-ultralow, metastatic breast cancer that is resistant to prior CDK4/6 inhibitor and endocrine therapy.
The names of the study drugs involved in this study are:
* Elacestrant (a type of selective estrogen receptor degrader) * Trastuzumab deruxtecan (a type of standard of care antibody drug conjugate)
Participants must have a histologically or cytologically confirmed diagnosis of HR+/HER2-low metastatic or unresectable locally advanced breast cancer, defined as ER ≥ 10%, any PR in the most recent sample and HER2-low (IHC 1+ or IHC 2+ and ISH non-amplified) or HER2-ultralow (IHC 0 and any membranous staining on any prior primary or metastatic sample). Cutoff values for positive/negative HER2 staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.76
Participants must have had prior CDK4/6 inhibitor and may have any number of prior endocrine based therapies in the metastatic setting.
Participants may have progressed on up to 1 prior line of prior chemotherapy or ADC in the metastatic setting.
Participants must have measurable disease per RECIST 1.1 criteria. See Section 11 for the definition of measurable disease. Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
Prior treatment with aatopoisomerase inhibitor antibody drug conjugate in any setting.
Prior treatment with an oral novel estrogen receptor degrader or modulator in the metastatic setting (SERD, SERM, PROTAC, or CERAN). Prior fulvestrant is allowed. A washout period of 7 days is required for any endocrine or targeted therapy. A washout period of 14 days is required for any chemotherapy.
Patients with known brain metastases that are symptomatic or that require therapy for symptom control are not eligible. Patients with stable or asymptomatic brain metastases are allowed. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 4 weeks before day 1 of study therapy will be excluded.
Receipt of any other investigational compound or device within 2 weeks of the first dose of treatment in this study.
Sequential
Elacestrant
DrugSelective estrogen receptor degrader (SERD), film-coated tablet, taken orally per protocol.
Trastuzumab Deruxtecan
DrugHER2-directed antibody-drug conjugate, vial, via intravenous (into the vein) infusion per standard of care
Recommended phase II dose (RP2D)
The RP2D is defined as the dose at which ≤ 3 out of 12 participants experience Dose Limiting Toxicities (DLT) during the first treatment cycle.
Objective Response Rate (ORR)
ORR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response as the best overall response.
ORR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
ORR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response as the best overall response.
Clinical Benefit Rate (CBR)
CBR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response, or stable disease for ≥ 24 weeks as the best overall response
CBR in Participants with ESR1-mutant endocrine- and CDK 4/6 inhibitor-resistant HR+/HER2-low of HER2-ultralow metastatic cancer
CBR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response, or stable disease for ≥ 24 weeks as the best overall response
Median progression-free survival (PFS)
PFS is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
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Kristina A. Fanucci
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Stemline Therapeutics, Inc.
Collaborator
