Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [¹⁴C]-LY3484356, Imlunestrant
LY3484356 · 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...
Top 20 of 87 competitors
LY3484356 is an investigational oral medicine being studied for breast cancer, including advanced and metastatic breast cancer, and for endometrial cancer. It is also being evaluated in Chinese participants with advanced breast cancer and in women with breast cancer before surgery. It is not yet approved for any use.
LY3484356 targets the estrogen receptor (ER). It is a small molecule designed to bind the estrogen receptor, the target class that drives many breast cancers. Trials of LY3484356 enroll biomarker-selected participants, meaning eligibility is tied to estrogen receptor status rather than an unselected population.
LY3484356 is being developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly sponsors the clinical program, including the Phase 1 studies in breast cancer and endometrial cancer.
LY3484356 is in Phase 1 clinical development. It is investigational and has not been approved by the FDA or any other regulator. The program includes three Phase 1 studies, one completed and two active but no longer recruiting, with a combined enrollment of 466 participants.
LY3484356 has been studied in NCT04188548, a Phase 1 trial in advanced or metastatic breast cancer and endometrial cancer across the United States, Australia, Belgium, France, Japan, South Korea, Spain and Taiwan, and in NCT04647487, a completed Phase 1 presurgical breast cancer study in the United States and five European countries. NCT05509790 is an active Phase 1 study in Chinese participants with advanced breast cancer.
Yes. [¹⁴C]-LY3484356 is an alternative name for LY3484356. The carbon-14 label denotes a radiolabeled form used in research, while LY3484356 is the name used for the clinical development program in breast cancer and endometrial cancer.