Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as (Z)-endoxifen, Topical 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 10% at Week 4, participant will be withdrawn and go on to surgery.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 10% at Week 4, participant will be withdrawn and go on to surgery.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 being developed for breast neoplasms, including estrogen-receptor-positive, HER2-negative invasive breast cancer, and for mammographic breast density. It is an investigational small molecule and is not yet approved for commercial use. Atossa Therapeutics is studying it in premenopausal women with ER+/HER2- breast cancer and in women with dense breast tissue.
Endoxifen targets the estrogen receptor, or ER. By acting on ER, it is designed to interfere with estrogen-driven signaling in breast tissue. This ER-directed mechanism underlies its development in estrogen-receptor-positive breast cancer and in mammographic breast density, where estrogen signaling contributes to breast tissue characteristics.
Endoxifen is being developed by Atossa Therapeutics, Inc., which trades under the ticker ATOS. The company is advancing the asset in oncology, with clinical work focused on breast neoplasms and mammographic breast density. Atossa holds orphan drug and rare pediatric disease designations for endoxifen.
Endoxifen is in Phase 2 clinical development. It is an investigational therapy and has not been approved by the FDA. Two Phase 2 studies have been conducted, one active and not recruiting and one completed, with a combined enrollment of 90 participants across the United States and Sweden.
Endoxifen has been studied in two Phase 2 trials. NCT05607004, titled (Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer, is active and not recruiting with 87 participants in the United States. NCT04616430, titled Topical Endoxifen in Women, is completed with 90 participants in Sweden.
Yes. Endoxifen is also known as (Z)-endoxifen and topical endoxifen. These names refer to the same investigational small molecule developed by Atossa Therapeutics. The (Z)-endoxifen form is being evaluated in premenopausal women with ER+/HER2- breast cancer, while topical endoxifen has been studied in women with mammographic breast density.