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Label indication INLURIYO is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 ( ESR1 )-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. FDA label
Also known as LY3484356
Imlunestrant · 6 trials · 6 indications
IDFS excluding second non-breast primary invasive cancers
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
PK: Plasma Concentration of LY3484356
Tumor tissue collected by biopsy is used to determine ER expression. ER expression is measured by immunohistochemistry (IHC) and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total ER H-score ranged from 0 to 300, where a higher score indicated stronger ER expression. Percent change in ER expression was defined as 100\*(ER expression on-treatment - ER expression pre-treatment)/(ER expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(ER expression on-treatment/ER expression pre-treatment).
Number of Participants with DLTs and DLT-Equivalent Toxicities
| Arm | Type | Description |
|---|---|---|
| Imlunestrant | EXPERIMENTAL | Imlunestrant administered orally. |
| Investigator's Choice of Endocrine Therapy | ACTIVE_COMPARATOR | Investigator's choice of tamoxifen, anastrozole, letrozole, or exemestane administered per local approved label. |
| Arm A: Imlunestrant | EXPERIMENTAL | Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met. |
| Arm B: Investigator's Choice of Endocrine Therapy | EXPERIMENTAL | Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met. |
| Arm C: Imlunestrant + Abemaciclib | EXPERIMENTAL | Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met. |
| Cohort 1 Arm A | EXPERIMENTAL | Imlunestrant will be given orally |
| Cohort 1 Arm B - Imlunestrant + Goserelin | EXPERIMENTAL | Imlunestrant will be given orally and goserelin will be given subcutaneously (SC) |
| Cohort 1 Arm C - Tamoxifen | ACTIVE_COMPARATOR | Tamoxifen will be given orally |
| Cohort 2 Arm A - Imlunestrant | EXPERIMENTAL | Imlunestrant will be given orally |
| Cohort 2 Arm B - Tamoxifen | ACTIVE_COMPARATOR | Tamoxifen will be given orally |
| LY3484356 Dose Level 1 | EXPERIMENTAL | Administered orally. |
| LY3484356 Dose Level 2 | EXPERIMENTAL | Administered orally. |
| 200 milligrams (mg) LY3484356 | EXPERIMENTAL | Participants received 200 mg LY3484356 administered orally once daily for 15 days |
| 400 mg LY3484356 | EXPERIMENTAL | Participants received 400 mg LY3484356 administered orally once daily for 15 days |
| 800 mg LY3484356 | EXPERIMENTAL | Participants received 800 mg LY3484356 administered orally once daily for 15 days |
| Dose Escalation LY3484356 | EXPERIMENTAL | LY3484356 given orally. |
| Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI | EXPERIMENTAL | LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally. |
| Part B: Dose Expansion: Cohort E3: LY3484356 | EXPERIMENTAL | LY3484356 given orally. |
| Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus | EXPERIMENTAL | LY3484356 and everolimus given orally. |
| Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib | EXPERIMENTAL | LY3484356 and alpelisib given orally. |
| Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib | EXPERIMENTAL | LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib. |
| Part D: Dose Expansion: LY3484356 +/- Abemaciclib | EXPERIMENTAL | LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously. |
| Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab | EXPERIMENTAL | LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously. |
| Name | Type | Description |
|---|---|---|
| Imlunestrant | DRUG | Administered orally. |
| Tamoxifen | DRUG | Administered per local approved label. |
| Anastrozole | DRUG | Administered per local approved label. |
| Letrozole | DRUG | Administered per local approved label. |
| Exemestane | DRUG | Administered per local approved label. |
| Fulvestrant | DRUG | Administered IM. |
| Abemaciclib | DRUG | Administered orally. |
| Goserelin | DRUG | Given SC |
| Tamoxifen 20 mg | DRUG | Given orally |
| LY3484356 | DRUG | Administered orally. |
| Everolimus | DRUG | Administered orally |
| Alpelisib | DRUG | Administered orally |
| Trastuzumab | DRUG | Administered intravenously |
| Aromatase Inhibitor (AI) | DRUG | Anastrozole or Exemestane or Letrozole administered orally (physician choice) |
| Pertuzumab | DRUG | Administered intravenously |
Inclusion Criteria: * Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without evidence of distant metastasis. * Participants must have received at least 24 months but not more than 60 months of any adjuvant ET, from time of adjuvant ET initiation. * Participants may hav...
Imlunestrant is an investigational oral small molecule being developed by Eli Lilly and Company for breast neoplasms, specifically estrogen receptor-positive disease. It is a selective estrogen receptor degrader, or SERD, in the -estrant class. It is currently in Phase 3 clinical development and has not been approved by the FDA.
Imlunestrant is being studied for estrogen receptor-positive breast cancer, including ER+, HER2- early breast cancer and ER+, HER2- advanced or metastatic breast cancer. Trials include premenopausal women with early disease and broader adult populations with advanced disease. It remains investigational and is not approved for any use.
Imlunestrant targets the estrogen receptor, or ER. It belongs to the -estrant class, also known as selective estrogen receptor degraders, or SERDs. By acting on the estrogen receptor, it is designed to address estrogen receptor-positive breast cancer, and the clinical program selects patients based on this biomarker.
Imlunestrant is being developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly is running the clinical program, which includes Phase 2 and Phase 3 studies in estrogen receptor-positive breast cancer, including combinations with other endocrine and targeted agents.
Imlunestrant is in Phase 3 clinical development. Three trials are listed, all currently active, with no completed trials. Two are Phase 3 studies and one is a Phase 2 study. Imlunestrant is investigational and has not been approved by the FDA for any indication.
Imlunestrant is being studied in NCT05514054, a Phase 3 trial versus standard endocrine therapy in early breast cancer with 8,000 participants, and NCT04975308, a Phase 3 trial in ER+, HER2- advanced breast cancer testing imlunestrant, endocrine therapy, and imlunestrant plus abemaciclib. NCT07287098 is a Phase 2 study in premenopausal women with ER+, HER2- early breast cancer.