SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.

P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Aug 2024 --> Aug 2025

P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Mar 2024 --> Aug 2024

P1, N=31, Active, not recruiting, Eisai Inc. | Phase classification: P1b --> P1

P1/2, N=206, Completed, Eisai Inc. | Active, not recruiting --> Completed

Median number of prior therapies for mBC was 3, including fulvestrant (79%), CDK4/6 inhibitors (73%), and chemotherapies (42%). Among 6 pts with ESR1 Y537S, CBR was 83% with 1 PR. Conclusions H3B-6545 450 mg QD had a manageable safety profile and showed preliminary antitumor effect in pts with heavily pretreated, ER+, HER2-negative mBC.

P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2024

Compound ZD12 exhibited excellent antitumor potency and ERα degradation activity in both tamoxifen-sensitive and -resistant BC mice models, which are superior to fulvestrant. This study demonstrates the potential of these PROTACs as novel drug candidates for endocrine-resistant BC treatment.

P1/2, N=206, Active, not recruiting, Eisai Inc. | N=151 --> 206

P1/2, N=151, Active, not recruiting, Eisai Inc. | Trial completion date: Dec 2022 --> Oct 2023 | Trial primary completion date: Dec 2022 --> Oct 2023

P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Feb 2023 --> Nov 2023 | Trial primary completion date: Feb 2023 --> Nov 2023

P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

In the induction phase, pts will receive 4–6 PH FDC SC cycles (1200 mg P/600 mg H in the first cycle, followed by 600/600 mg every 3 weeks) + a taxane (investigator choice of docetaxel/paclitaxel)...ET (aromatase inhibitor/tamoxifen) will be allowed in the PH FDC SC-only arm...CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Clinicaltrials.gov number: NCT05296798.

Tamoxifen (TMX), a main drug for the treatment of ER-positive breast cancer in clinical, is a selective ER modulator (SERM)...In summary, these results provided a new insight into the mechanism of TMX-induced NAFLD. Moreover, it supported the combination of Fato and TMX for the treatment of ER-positive breast cancer to reduce the adverse effect of TMX in clinical.

P1/2, N=170, Active, not recruiting, H3 Biomedicine Inc. | Trial completion date: Jun 2023 --> Dec 2022 | Trial primary completion date: Jun 2023 --> Dec 2022

H3B-6545 demonstrates significant activity and superiority over standard-of-care fulvestrant across a panel of ERαWT and ERαMUT palbociclib sensitive and resistant models. In summary, the compelling preclinical activity of H3B-6545 supports its further development for the potential treatment of endocrine therapy-resistant ERα+ breast cancer harboring wild-type or mutant ESR1, as demonstrated by the ongoing clinical trials (NCT03250676, NCT04568902, NCT04288089). H3B-6545 is an ERα covalent antagonist that exhibits encouraging preclinical activity against CDK4/6i naïve and resistant ERαWT and ERαMUT tumors.

P1/2, N=170, Active, not recruiting, H3 Biomedicine Inc. | Recruiting --> Active, not recruiting

P1b, N=36, Active, not recruiting, H3 Biomedicine Inc. | Recruiting --> Active, not recruiting

P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: Sep 2022 --> Jun 2023 | Trial primary completion date: Mar 2022 --> Jun 2023

P1, N=33, Recruiting, Eisai Co., Ltd. | N=18 --> 33

P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: May 2025 --> Sep 2022 | Trial primary completion date: Nov 2024 --> Mar 2022

P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: Jan 2024 --> May 2025 | Trial primary completion date: Jan 2022 --> Nov 2024

One patient had an abnormal heart rate recovery on exercise testing at screening and again while on treatment. Conclusions In a thorough cardiac safety analysis, applying routine electrocardiograms, 24-hour Holter monitoring, and exercise testing, no clinically relevant cardiac effects were observed with 100 mg giredestrant (a higher dose than the phase III 30 mg dose).

Conclusions The study will proceed to the primary analysis. We expect to see encouraging results based on the favorable interim analysis data that demonstrated the superior activity of giredestrant, an oral selective estrogen receptor antagonist and degrader, compared with anastrozole.

Prior therapy in the metastatic setting included fulvestrant (93%), CDK4/6 inhibitors (79%), aromatase inhibitors (64%), and chemotherapy (29%). The combination of H3B-6545 (up to 300 mg dose) and palbociclib (up to 125 mg dose) was well-tolerated and demonstrated preliminary anti-tumor activity in heavily pretreated pts with ER+, HER2- mBC. ClinicalTrials.gov Identifier : NCT04288089.

H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was consistent across the various subgroups. Tumors harboring the constitutionally active ESR1 Y537S mutation may present higher ERα activity, and consequently enrich for luminal A traits and demonstrate greater lineage dependence on ERα.

P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Apr 2022 --> Feb 2023 | Trial primary completion date: Apr 2022 --> Feb 2023

P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Jan 2022 --> Apr 2022 | Trial primary completion date: Jan 2022 --> Apr 2022

At low doses, 35 induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1 mutant PDX or a wild-type ERα tumor model. Currently, 35 is being evaluated in Phase III clinical trials.

H3B-6545, in combination with palbociclib, was well-tolerated.

Prior CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, and chemotherapy were received by 85%, 80%, 72%, and 50% of the pts, respectively . H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients . Clinical activity was observed in pts with ESR1 mutations.

P1/2, N=106, Recruiting, EnhancedBio USA Inc. | Not yet recruiting --> Recruiting | Initiation date: Feb 2021 --> May 2021

P1/2, N=106, Not yet recruiting, EnhancedBio USA Inc.

P1, N=18, Recruiting, Eisai Co., Ltd. | Not yet recruiting --> Recruiting

Prior CDK4/6 inhibitors, fulvestrant, and chemotherapy were received by 87%, 71%, and 54% of the pts, respectively. Median PFS, in all pts and in pts with clonal ESR1 Y537S was 3.7 months and 7.3 months, respectively. Conclusions : H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients including those with a constitutively active clonal ESR1 Y537S mutation.

H3B-6545 PK profiles in breast cancer patients were well described by a one-compartment disposition model with no significant effect of demographics, liver and renal function. When administered with a high fat meal, H3B-6545 exposure was modestly increased.

P1, N=18, Not yet recruiting, Eisai Co., Ltd.

P1/2, N=148, Recruiting, H3 Biomedicine Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2022 --> Jan 2024 | Trial primary completion date: Jul 2020 --> Jan 2022

P1b, N=36, Recruiting, H3 Biomedicine Inc. | Not yet recruiting --> Recruiting

The effect of ICI 182,780 on increasing acidic vesicular organelles in estrogen receptor-positive breast cancer cells appears to be associated with its inhibitory effect on estrogen receptors, and GPER does notseem to be involved. Understanding these mechanisms may guide further investigations of these receptors' involvement in cellular processes of breast cancer resistance.