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Also known as (Z)-endoxifen
endoxifen · 2 trials · 5 indications
(Z)-endoxifen steady-state plasma concentrations (Css) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
For analysis Cohort A (subjects that have a baseline Ki-67\>10%): the primary objective is to determine whether the Week 4 Ki-67 ≤ 10% rate is at least 65% among premenopausal women with primary estrogen receptor positive (ER+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer.
For analysis Cohort B (subjects have baseline Ki-67≤ 10%): the primary objective is to determine the objective tumor response rate at 24 weeks among premenopausal women with ER+, HER2-, Ki-67 ≤ 10% breast cancer receiving (Z) endoxifen plus goserelin.
Change, on an individual level, in mammographic breast density, measured at 6 months or when exiting from the study (baseline screening mammography)
| Arm | Type | Description |
|---|---|---|
| PK Cohort | EXPERIMENTAL | (Z)-endoxifen capsules orally once daily for 4 weeks. Initial (Z)-endoxifen dose evaluated will be 40 mg with an option to evaluate 20 mg or 80 mg. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery. |
| Treatment Cohort - Single Treatment Arm | EXPERIMENTAL | (Z)-endoxifen 40mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days. (Z)-endoxifen 40mg dose based on results of PK Cohort. If Ki-67 ≤ 10% at Week 4, continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. And then go on to surgery within 3 weeks of Cycle 6 day 26. If Ki-67 \> 10% at Week 4, participant will complete early termination assessments. |
| PK Cohort 80 mg | EXPERIMENTAL | (Z)-endoxifen 80 mg capsules orally once daily for 4 weeks. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery. |
| PK Cohort 80 mg + OFS | EXPERIMENTAL | (Z)-endoxifen 80 mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery. |
| Control | PLACEBO_COMPARATOR | Topical Placebo:Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil |
| Topical Endoxifen 10mg/breast/day | ACTIVE_COMPARATOR | 10 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil |
| Topical Endoxifen 20mg/breast/day | ACTIVE_COMPARATOR | 20 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil |
| Name | Type | Description |
|---|---|---|
| (Z)-endoxifen | DRUG | (Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules). |
| goserelin | DRUG | goserelin 3.6 mg subcutaneous implant |
| Topical endoxifen | DRUG | topical solution |
| Placebo | DRUG | topical |
Inclusion Criteria: 1. Female sex assigned at birth. Female to male transgender individuals who have not had any hormonal therapy may be considered for the trial after review and approval from the medical monitor and study sponsor. 2. Age 18 years or older 3. Not lactating, pregnant, or planning to...
Endoxifen is an investigational small molecule being studied for use in breast neoplasms and mammographic breast density. It is being evaluated in premenopausal women with ER+/HER2- breast cancer and in women with high mammographic breast density. The drug is in Phase 2 clinical development.
Endoxifen is an active metabolite of tamoxifen and acts as a selective estrogen receptor modulator. It targets estrogen receptors, which are involved in the growth of estrogen-receptor-positive breast cancers. By modulating these receptors, endoxifen may help treat ER+ breast cancer and reduce breast density.
Endoxifen is being developed by Atossa Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol ATOS. The company is conducting clinical trials to evaluate the drug for breast cancer and mammographic breast density indications.
Endoxifen is currently in Phase 2 clinical development. It has received orphan drug designation and rare pediatric disease designation from the FDA. The drug is investigational and has not been approved by the FDA for any use.
Endoxifen has two Phase 2 trials. NCT04616430, completed in Sweden, enrolled 90 women with mammographic breast density. NCT05607004, active in the United States, is studying (Z)-endoxifen in 87 premenopausal women with ER+/HER2- breast cancer. Both trials are controlled but not randomized or double-blind.
Yes, endoxifen is also known as (Z)-endoxifen. The (Z)-isomer is the specific form being studied in clinical trials, including NCT05607004 for breast cancer treatment. Both names refer to the same investigational drug developed by Atossa Therapeutics.