EMBER: A Phase Ia/Ib Study of LY3484356 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers

Study Identifier:
J2J-MC-JZLA
CT.gov Identifier:
NCT04188548
EudraCT Identifier:
2019-003581-41
EU Trial (CTIS) Number:
2023-506785-32-00
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To evaluate LY3484356 alone or in combination with abemaciclib in participants with advanced or metastatic breast cancer.

To present the phase 1b dose expansion of imlunestrant with abemaciclib + or - aromatase inhibitor (AI) in EMBER

Key endpoints included safety and tolerability, PK, objective response rate (ORR) per RECIST v1.1 (ORR: complete response [CR] or partial response [PR]) in patients with measurable disease), and clinical benefit rate (CBR: CR or PR, or stable disease ≥24 weeks) in patients enrolled ≥24

weeks prior to data cut.

To determine the RP2D, safety, pharmacokinetics, and efficacy of imlunestrant as monotherapy and in combination with targeted therapy for ER+ ABC and endometrioid cancer.

The study focused on reporting the results of ER+/HER2- ABC.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
  • Endometrial
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18 - 65 Years
    Study Drug
  • Drug: Experimental: Dose Escalation LY3484356
    • Read More
  • Drug: Experimental: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab
  • Drug: SABCS 2020:
  • Drug: ASCO 2021:
  • Drug: Dose-escalation followed an i3+3 design with 5 dose levels (200 mg -1200 mg) evaluated.
  • Drug: 2022 ASCO:
  • Drug: SABCS 2022:
  • Drug: Dose Escalation part:
  • Drug: Combination part:
  • Drug: Drug: Abemaciclib
  • Drug: Drug: Aromatase Inhibitor (AI)
  • Drug: Part B
  • Drug: Drug: Everolimus
  • Drug: Part C
  • Drug: Drug: Trastuzumab
  • Drug: Part D
  • Drug: Pts were randomized to imlunestrant (400mg po daily) + trastuzumab (H), with or without (±) abemaciclib (Part C) or received maintenance treatment with imlunestrant + H + pertuzumab (P) (Part E), at standard doses in 21-day cycles.
  • Drug: The study uses an i3+3 dose escalation design, followed by dose expansion with imlunestrant alone or in combination with abeciclib (± aromatase inhibitor [AI]), everolimus, or apellibus. Imlunestrant is given orally once daily and concurrently with the combination drug according to the relevant label.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    Inclusion criteria
    • All study parts:
    • Participants must be willing to provide adequate archival tissue sample
    • Participants must be willing to use highly effective birth control
    • Participants must have adequate organ function
    • Participants must be able to swallow capsules
    • Dose escalation- Participants must have one of the following:
    • Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable or metastatic disease who have had the following:
    • Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy.
    • Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine therapy in the advanced/metastatic setting, and must have received a prior CDK4/6 inhibitor
    • Cohort E4: No prior everolimus.
    • Cohort E5: No prior alpelisib and must have a phosphatidylinositol 3-kinase catalytic a (PIK3Ca) mutation as determined by local testing.
    • Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer with evidence of locally advanced unresectable or metastatic disease who have had at least 2 HER2-directed therapies in any setting.
    • Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase inhibitor therapy.
    • Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable, or metastatic disease.
    • Part E: Participants must have received induction taxane chemotherapy combined with trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and must not have progressed on this regimen.
    • Part E: Participants must not have received more than 1 HER2-directed regimen or any endocrine therapy for advanced disease or any prior CDK4/6 inhibitor therapy.
    • Participants with ER+/HER2- breast cancer enrolled in this study must have had evidence of clinical benefit while on endocrine therapy for at least 24 months in the adjuvant setting or at least 6 months in the advanced/metastatic setting or have untreated de novo metastatic breast cancer
    Exclusion criteria
    • Participants must not have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled
    • Participants must not have another serious medical condition
    • Participants must not have cancer of the central nervous system that is unstable
    • Participants must not be pregnant or breastfeeding
    • Have symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.
    • Have a serious concomitant systemic disorder
    • Have pre-existing nausea, vomiting or diarrhea > grade 1 per CTCAE5.0.
    • Have visceral crisis.
    • Have inflammatory breast cancer .
    • Have an serious cardiac condition
    • Diagnosed and/or treated malignancy within 3 years prior to enrolment.
    • Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
    • Patients should refrain from consuming grapefruit, grapefruit juice, and grapefruit-containing products while on study due to the effect on CYP3A4 -

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Endometrial
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Amita Patnaik
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Endometrial