H3B-6545

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

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

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

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

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, 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

P1b, N=36, Not yet recruiting, H3 Biomedicine Inc.

P1/2, N=127, Active, not recruiting, H3 Biomedicine Inc. | Recruiting --> Active, not recruiting | Trial completion date: May 2020 --> Jan 2022 | Trial primary completion date: Nov 2019 --> Jul 2020