Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LY3484356 · 5 trials · 6 indications
PK: Plasma Concentration of LY3484356
The percentage of the total radioactive dose administered that was excreted in feces = (amount of radioactive dose recovered in feces / total radioactive dose administered) \* 100.
The percentage of the total radioactive dose administered that was excreted in urine = (amount of radioactive dose recovered in urine / total radioactive dose administered) \* 100.
PK: Bioavailability is defined as the percentage of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability, calculated for plasma LY3484356 as "F %= \[AUC (0-∞), LY3484356\] × \[Dose, \[14C\]-LY3484356\] / \[AUC (0-∞), \[14C\]-LY3484356\] × \[Dose, LY3484356\] ×100%'' Higher percent indicates better absorption of drug into the body.
PK: AUC\[0-∞\] of LY3484356
PK: AUC\[0-∞\] of LY3484356
PK: AUC\[0-∞\] of LY3484356
AUC\[0-∞\] of LY3484356
PK: Tmax of LY3484356
PK: Tmax of LY3484356
PK: Tmax of LY3484356
Tmax of LY3484356
Cmax of LY3484356
Cmax of LY3484356
Cmax of LY3484356
Cmax 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 |
|---|---|---|
| LY3484356 Dose Level 1 | EXPERIMENTAL | Administered orally. |
| LY3484356 Dose Level 2 | EXPERIMENTAL | Administered orally. |
| [¹⁴C]-LY3484356 (Part 1) | EXPERIMENTAL | Participants received a single oral dose of 400 mg Carbon 14 labelled \[¹⁴C\]-LY3484356 following an overnight fast of at least 10 hours on Day 1. |
| LY3484356 + [¹⁴C]-LY3484356 (Part 2) | EXPERIMENTAL | Participants received a single oral dose of 400 mg LY3484356 following an overnight fast of at least 10 hours on Day 1, followed 4 hours later by a single dose of less than 100 microgram (μg) \[¹⁴C\]-LY3484356 (actual ranged from 44.55 to 45.95 μg), as an intravenous (IV) infusion on day 1. |
| Cohort 1 Sequence 1: 400 mg LY3484356 Fasted/ 400 mg LY3484356 Fed | EXPERIMENTAL | Participants were randomized (1:1) to 1 of 2 treatment sequences; LY3484356 administered as single doses orally with (fed) or without food (fasted) as below: Period 1: Single dose of 400 mg LY3484356 in the fasted state. Period 2: Single dose of 400 mg LY3484356 in the fed state. There was a washout period of 4 days between doses of LY3484356 |
| Cohort 1 Sequence 2: 400 mg LY3484356 Fed/ 400 mg LY3484356 Fasted | EXPERIMENTAL | Participants were randomized (1:1) to 1 of 2 treatment sequences; LY3484356 administered as single doses orally with (fed) or without food (fasted) as below: Period 1: Single dose of 400 mg LY3484356 in the fed state. Period 2: Single dose of 400 mg LY3484356 in the fasted state. There was a washout period of 4 days between doses of LY3484356. |
| Cohort 2: LY3484356 + Omeprazole | EXPERIMENTAL | Participants received single dose of LY3484356 and a single dose of omeprazole alone and in combination administered orally as below: Day 1: 400 mg LY3484356 alone Days 5 to 8: 40 mg omeprazole alone once daily Day 9: 400 mg LY3484356 + 40 mg omeprazole once There was a washout period of 8 days between doses of LY3484356. |
| Cohort 3: LY3484356 + Itraconazole | EXPERIMENTAL | Participants received single dose of LY3484356 and a single dose of Itraconazole alone and in combination administered orally as below: Day 1: 200 mg LY3484356 alone Days 5 to 9: 200 mg itraconazole alone (twice on Day 5 \[dose separated by approximately 12 hours\], then once daily on Days 6 through 9) Day 10: 200 mg LY3484356 + 200 mg itraconazole once (coadministered with the morning dose) Days 11 to 16: 200 mg itraconazole alone once daily. There was a washout period of 9 days between doses of LY3484356. |
| Cohort 4: LY3484356 + Carbamazepine | EXPERIMENTAL | Participants received single dose of LY3484356 and a single dose of carbamazepine alone and in combination administered orally as below: Day 1: 400 mg LY3484356 alone Days 6 to 8: 100 mg carbamazepine BID alone Days 9 to 11: 200 mg carbamazepine BID alone Days 12 to 17: 300 mg carbamazepine BID alone Day 18: 300 mg carbamazepine BID + 400 mg LY3484356 (coadministered with morning dose) Days 19 to 22: 300 mg carbamazepine BID alone Day 23: 300 mg carbamazepine alone (morning dose only). There was a washout period of 17 days between doses of LY3484356. |
| Cohort 5: Carbamazepine + Midazolam | EXPERIMENTAL | Participants received single dose of Carbamazepine and a single dose of midazolam alone and in combination administered orally as below: Day 1: 1.2 mg midazolam alone Days 2 to 4: 100 mg carbamazepine BID alone Days 5 to 7: 200 mg carbamazepine BID alone Days 8 to 10: 300 mg carbamazepine BID alone Day 11: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose) Days 12 to 13: 300 mg carbamazepine BID alone Day 14: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose). |
| 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 |
|---|---|---|
| LY3484356 | DRUG | Administered orally. |
| [¹⁴C]-LY3484356 | DRUG | Administered orally. |
| [¹⁴C]-LY3484356 (IV) | DRUG | Administered IV. |
| Omeprazole | DRUG | Administered orally. |
| Itraconazole | DRUG | Administered orally. |
| Carbamazepine | DRUG | Administered orally. |
| Midazolam | DRUG | Administered orally. |
| Abemaciclib | 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: * Native Chinese participants must be of an acceptable age to provide informed consent * Have locally advanced (not amenable to curative treatment by surgery) or metastatic disease and be an appropriate candidate for experimental therapy in the judgment of the investigator, afte...
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LY3484356 is an investigational small molecule being studied for the treatment of breast cancer, including advanced and metastatic breast cancer, as well as endometrial cancer. It is also being evaluated in healthy female participants for research purposes. The drug is currently in Phase 1 clinical development.
LY3484356 targets the estrogen receptor (ER). As an estrogen receptor-targeting agent, it is being investigated for its potential role in treating hormone-related cancers such as breast cancer. The drug is designed to interact with this receptor, which is a key driver in certain types of breast cancer.
LY3484356 is being developed by Eli Lilly and Company, a pharmaceutical company listed on the stock exchange under the ticker symbol LLY. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational drug in patients with breast cancer and other conditions.
LY3484356 is in Phase 1 clinical development. It is an investigational drug, meaning it has not yet been approved by regulatory authorities. The ongoing Phase 1 trials are designed to assess the drug's safety, tolerability, and preliminary efficacy in participants with breast cancer and healthy volunteers.
LY3484356 is being studied in several Phase 1 clinical trials. NCT04188548 is an active trial in participants with advanced or metastatic breast cancer or endometrial cancer. NCT04647487 is a completed trial in women with breast cancer before surgery. NCT04840888 and NCT04991766 are completed trials in healthy female participants.
LY3484356 is also known as imlunestrant. This alternative name is used in some clinical and research contexts. The drug is being developed by Eli Lilly and Company for the treatment of breast cancer and other conditions. Both names refer to the same investigational compound.