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    DRUG:

    H3B-6545

    i
    Other names: H3B-6545, H3B 6545, H3B6545, SERCA H3B-6545
    Company:
    Eisai
    Drug class:
    Selective estrogen receptor α inhibitor
    Related drugs:
    14d
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Aug 2025 --> Mar 2026
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    30d
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2024 --> Mar 2026 | Trial primary completion date: Aug 2024 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • HER-2 negative + ER positive
    |
    H3B-6545
    3ms
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Aug 2024 --> Aug 2025
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    9ms
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=31, Active, not recruiting, Eisai Inc. | Trial completion date: Mar 2024 --> Aug 2024
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    9ms
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=31, Active, not recruiting, Eisai Inc. | Phase classification: P1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    12ms
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=206, Completed, Eisai Inc. | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    1year
    Phase I study of H3B-6545 in patients (pts) with estrogen receptor-positive (ER+) breast cancer (ESMO Asia 2023)
    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.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S
    |
    fulvestrant • H3B-6545
    1year
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2024
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    over1year
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=206, Active, not recruiting, Eisai Inc. | N=151 --> 206
    Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    almost2years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=151, Active, not recruiting, Eisai Inc. | Trial completion date: Dec 2022 --> Oct 2023 | Trial primary completion date: Dec 2022 --> Oct 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    almost2years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Feb 2023 --> Nov 2023 | Trial primary completion date: Feb 2023 --> Nov 2023
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    2years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=33, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    over2years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    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
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    over2years
    Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. (PubMed, Mol Cancer Ther)
    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.
    Preclinical • Journal
    |
    ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    ER mutation • ESR1 mutation
    |
    Ibrance (palbociclib) • fulvestrant • H3B-6545
    over2years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=170, Active, not recruiting, H3 Biomedicine Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    over2years
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1b, N=36, Active, not recruiting, H3 Biomedicine Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    over2years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: Sep 2022 --> Jun 2023 | Trial primary completion date: Mar 2022 --> Jun 2023
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G • ESR1 mutation
    |
    H3B-6545
    almost3years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=33, Recruiting, Eisai Co., Ltd. | N=18 --> 33
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    3years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: May 2025 --> Sep 2022 | Trial primary completion date: Nov 2024 --> Mar 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G
    |
    H3B-6545
    3years
    H3B-6545-A001-101: Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=170, Recruiting, H3 Biomedicine Inc. | Trial completion date: Jan 2024 --> May 2025 | Trial primary completion date: Jan 2022 --> Nov 2024
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G
    |
    H3B-6545
    3years
    H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer, phase 1b study (SABCS 2021)
    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.
    Clinical • P1 data • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    Ibrance (palbociclib) • fulvestrant • H3B-6545
    3years
    H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer - A phase II study (SABCS 2021)
    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.
    P2 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER mutation • ER Y537S
    |
    H3B-6545
    3years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Apr 2022 --> Feb 2023 | Trial primary completion date: Apr 2022 --> Feb 2023
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    3years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Jan 2022 --> Apr 2022 | Trial primary completion date: Jan 2022 --> Apr 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    over3years
    [VIRTUAL] Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer. (ASCO 2021)
    H3B-6545, in combination with palbociclib, was well-tolerated.
    Clinical • P1 data • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    over3years
    [VIRTUAL] Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. (ASCO 2021)
    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 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER mutation • ER Y537S • ER D538G
    |
    fulvestrant • H3B-6545
    4years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, Eisai Co., Ltd. | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    4years
    [VIRTUAL] Phase I/II trial of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (SABCS 2020)
    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.
    P1/2 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER mutation • ER Y537S
    |
    fulvestrant • H3B-6545
    4years
    [VIRTUAL] Pharmacokinetics of H3B-6545 in patients with locally advanced or metastatic estrogen receptor-positive HER2 negative breast cancer (ER+ and HER2- BC) (SABCS 2020)
    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.
    Clinical • PK/PD data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 positive • ER positive • HER-2 negative • ER positive + HER-2 negative
    |
    H3B-6545
    4years
    Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, Eisai Co., Ltd.
    Clinical • New P1 trial
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    H3B-6545
    over4years
    Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    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
    Clinical • Enrollment open • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G
    |
    H3B-6545
    over4years
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1b, N=36, Recruiting, H3 Biomedicine Inc. | Not yet recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    almost5years
    H3B-6545-G000-102: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (clinicaltrials.gov)
    P1b, N=36, Not yet recruiting, H3 Biomedicine Inc.
    Clinical • New P1 trial • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • H3B-6545
    almost5years
    Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    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
    Clinical • Enrollment closed • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ER Y537S • ER D538G
    |
    H3B-6545