EMBER:A Study of LY3484356 in Patients with ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers

Phase 1

• Conditions: ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003581-41-BE
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-07
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

6.Have histological or cytological diagnosis of one of the following:
- Phase 1a and Phase 1b Parts A and B: ER+ and HER2- breast cancer with evidence of locally advanced unresectable or metastatic disease
- Phase 1b Part C: ER+ and HER2+ breast cancer with evidence of locally advanced unresectable or metastatic disease
- Phase 1a and Phase 1b Part D: ER+ recurrent, persistent, or metastatic EEC
- For breast cancer patients, ER and HER2 status assessed from the most recent tissue biopsy taken at the time of presentation with recurrent or metastatic disease.
oTo fulfill the requirement for ER+ disease by local testing, =1% of tumor cell nuclei must be immunoreactive by immunohistochemistry defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Allison et al. 2020).
oTo fulfill the requirement of HER2- disease by local testing on primary disease specimen, tumor must be HER2- according to ASCO/CAP guidelines for HER2 testing (Wolff et al. 2018).
oTo fulfill the requirement of HER2+ disease, tumor must be HER2+ as defined by in situ hybridization or FISH or IHC methodology in the relevant ASCO/CAP HER2 guidelines (Wolff et al. 2018).
- For EEC patients, ER+ status determined by local testing.

34.Phase 1a and Phase 1b Parts A and B: breast cancer patients must have either:
a. Untreated de novo metastatic disease or
b. Demonstrated sensitivity to prior ET by 1 of the following:
i. Documented clinical benefit (complete response [CR], PR, stable disease [SD] =24 weeks) to at least 1 prior ET in the metastatic setting or
ii. At least 24 months of adjuvant ET prior to recurrence, with the exception of patients who discontinued prior adjuvant ET earlier for reasons other than progressive disease.

35.Prior therapies received in the metastatic setting:
- Phase 1a: breast cancer patients may have had up to 3 prior regimens (no restrictions on types of prior therapies)
- Phase 1b Part A: patients may have had up to 1 prior regimen of any kind for advanced/mBC but must not have received a prior CDK4/6 inhibitor.
- Phase 1b Part B: patients may have had up to 2 prior regimens, no more than 1 of which may be ET and must have received a prior CDK4/6 inhibitor or be deemed inappropriate for or refused such therapy.
oCohort E4: patients must not have had prior everolimus
oCohort E5: patients must have a known and activating PIK3Ca mutation as determined by local testing and must not have had prior alpelisib
- Phase 1b Part C: patients must have had at least 2 HER2-directed regimens in any setting. Patients must have left ventricular ejection fraction (LVEF) of 50% or higher at baseline (determined by echocardiography or multigated acquisition scanning). Patients must not have received prior CDK4/6 inhibitor therapy or fulvestrant.
- Phase 1a EEC patients and Phase 1b Part D: patients must have progressed after platinum-containing chemotherapy, be deemed inappropriate for or declined platinum-containing chemotherapy, and must not have had prior fulvestrant or AI therapy.

7.Measurability of Lesions:
a) Breast cancer patients must have one of the following as defined by RECIST v1.1
(Eisenhauer et al. 2009):
?- Measurable disease
?- Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may include any of the following:
i.blastic bone lesions

Exclusion Criteria

1. Have symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.
2. Have a serious concomitant systemic disorder
3. Have pre-existing nausea, vomiting or diarrhea > grade 1 per CTCAE5.0.
4. Have visceral crisis.
5. Have inflammatory breast cancer .
6. Have an serious cardiac condition
7. Diagnosed and/or treated malignancy within 3 years prior to enrolment.
8.Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
9. Patients should refrain from consuming grapefruit, grapefruit juice, and grapefruit-containing products while on study due to the effect on CYP3A4 –

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified