ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer

Plain English Summary

ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer is a Phase 2 clinical trial sponsored by Sarah Sammons, MD studying Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female. This trial is testing a combination of two drugs, elacestrant and trastuzumab deruxtecan, to see if they are safe and effective for treating a specific type of advanced breast cancer. It is for patients with hormone receptor-positive (HR+), HER2-low or HER2-ultralow metastatic breast cancer that has stopped responding to CDK4/6 inhibitor and endocrine therapies. Participation involves receiving the study drugs, with regular check-ups and tests to monitor your health and the cancer's response. Alternative treatments may include other chemotherapy, targeted therapies, or endocrine therapies, depending on the patient's specific situation and prior treatments. The trial aims to enroll 65 participants.

Official Summary

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)

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with metastatic or locally advanced HR+/HER2-low or HER2-ultralow breast cancer that has progressed after CDK4/6 inhibitor and endocrine therapy. Must have measurable disease and known ESR1 mutation status. Individuals must be 18 years or older with adequate organ and marrow function. Women must be postmenopausal or premenopausal women on GnRH agonist therapy; men are also eligible. This trial is studying Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures, such as the recommended phase II dose and objective response rate, will tell us how well the combination of elacestrant and trastuzumab deruxtecan works to shrink tumors The specific primary outcome measures are: Recommended phase II dose (RP2D) (Assessed at the end of the first treatment cycle, Day 21.); Objective Response Rate (ORR) (assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months). 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 new treatment options for patients with advanced breast cancer that has become resistant to standard therapies, aiming to improve outcomes in a challenging-to- Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in metastatic breast cancer, potentially offering a new therapeutic option in a market with ongoing innovation in targeted therapies and antibody-drug conju 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 trastuzumab deruxtecan, and how this trial fits with other treatment options. Participation involves regular clinic visits for drug administration, blood tests, imaging scans, and assessments of your overall health and any side effects. Be prepared to discuss your medical history, current medications, and any symptoms you are experiencing with the study team. This trial is currently recruiting participants. The trial is being conducted at 1 site. 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: 65 participants

Interventions

• DRUG: Elacestrant — Selective estrogen receptor degrader (SERD), film-coated tablet, taken orally per protocol.
• DRUG: Trastuzumab Deruxtecan — HER2-directed antibody-drug conjugate, vial, via intravenous (into the vein) infusion per standard of care

Primary Outcomes

• Recommended phase II dose (RP2D) (Assessed at the end of the first treatment cycle, Day 21.)
• Objective Response Rate (ORR) (assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months)

Secondary Outcomes

• ORR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer (assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months)
• Clinical Benefit Rate (CBR) (assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months)
• CBR in Participants with ESR1-mutant endocrine- and CDK 4/6 inhibitor-resistant HR+/HER2-low of HER2-ultralow metastatic cancer (assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months)
• Median progression-free survival (PFS) (assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months)
• Median PFS in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer (assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months)

Full Eligibility Criteria

Inclusion Criteria:

* 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 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 without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiographic evaluation.
* Participants must have had prior CDK4/6 inhibitor and either:

  * Disease progression on or within 12 months of endocrine therapy plus a CDK4/6 inhibitor in the adjuvant setting
  * One previous line of endocrine therapy in metastatic setting if disease progression within 6 months of first-line CDK4/6 plus endocrine treatment for metastatic disease or disease recurrence within 24 months after initiation of adjuvant endocrine therapy
  * Two previous lines of endocrine therapy in the metastatic with or without a targeted therapy (such as but not limited to CDK4/6, mTOR, or PI3K inhibitors) administered for the treatment of metastatic disease.
  * Of note with regards to the 2 lines of previous endocrine therapy requirement:- Disease recurrence while on the first 24 months of adjuvant endocrine therapy will be considered a line of therapy; these patients will only require 1 line of endocrine therapy in the metastatic setting.

    * Single-agent PARP inhibitor therapy is not considered a line of endocrine therapy but is allowed.
    * Changes in dosing schedules, or discontinuations/restarting of the same drugs of the addition of a targeted therapy to an endocrine therapy without progression (e.g., adding a CDK4/6 inhibitor to a current aromatase inhibitor regimen) will not be considered separate lines of therapy.
* Participants may have not received 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.
* Participants must have known ESR1 mutation status in tumor or ctDNA within 6 months of enrollment to the trial.
* Women or men age ≥18 years are eligible.
* ECOG performance status ≤ 2.
* Participants must meet the following organ and marrow function as defined below:

  * Absolute neutrophil count ≥ 1,500/µL
  * Platelets ≥ 100,000/µL
  * Hemoglobin ≥ 9.0 g/dL
  * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2 x ULN in patients with documented Gilbert's syndrome)
  * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional ULN (or \< 5 x ULN in patients with liver metastases)
  * Creatinine ≤ 1.5 x institutional ULN OR
  * Calculated creatinine clearance ≥ 45 mL/min via the Cockcroft-Gault formula for participants with creatinine levels above institutional ULN
  * Participants with a history of central nervous system (CNS) metastases are eligible if: Stable or untreated, asymptomatic brain metastases not needing immediate local therapy. For patients with untreated CNS lesions \> 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment.
  * Previously treated brain metastases

    * a. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator
    * b. Patients treated with CNS local therapy for newly identified lesions may be eligible to enroll if all of the following criteria are met: i. Time since WBRT is ≥ 14 days prior to first dose of treatment, time since SRS is ≥ 7 days prior to first dose of treatment, or time since surgical resection is ≥ 14 days
* Women must be postmenopausal, which is defined as any of the following:

  * Age ≥ 60 years
  * Age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH, and estradiol in the postmenopausal range per local normal range
  * Premenopausal women must be on GnRH agonist prior to study entry are eligible. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment.
  * Status-post bilateral oophorectomy - After adequate healing post-

Trial Locations

• Dana-Farber Cancer Institute, Boston, Massachusetts, United States

Frequently Asked Questions

Related Conditions

• Metastatic Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Low Breast Cancer
• HER2-Ultralow Breast Cancer
• Endocrine-Resistant Breast Cancer
• CDK4/6 Inhibitor Resistance
• Advanced Breast Cancer
• Metastatic Cancer
• Oncology
• Breast Cancer

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