H3B-6545 / Eisai - LARVOL DELTA

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 | Completed | Sponsor: Eisai Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Oct 2025 | Trial primary completion date: Mar 2026 ➔ Oct 2025

Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer. (PubMed, Breast Cancer Res) - No abstract available

Journal • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase I study of H3B-6545 in patients with estrogen receptor-positive breast cancer. (PubMed, ESMO Open) - P1 | "H3B-6545 at 450 mg QD was tolerated and showed preliminary antitumor effects in Japanese patients with ER-positive, HER2-negative mBC, particularly for those with ESR1 mutations."

Journal • P1 data • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Trial completion date: Aug 2025 ➔ Mar 2026

Combination therapy • Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: 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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Trial completion date: Aug 2024 ➔ Aug 2025

Combination therapy • Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

H3B-6545 + palbociclib in patients (pts) with locally advanced/metastatic estrogen receptor-positive (ER+), HER2 negative (–) breast cancer (BC). (ASCO 2024) - P1 | "H3B-6545 300 mg + palbo (100/125 mg) had manageable safety and encouraging preliminary antitumor activity. Further studies are warranted to identify the RP2D."

Clinical • Metastases • Anemia • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive (ER+), HER2 negative (–) breast cancer (BC). (ASCO 2024) - P1/2 | "H3B-6545 had a low rate of G ≥3 TEAEs and showed clinically meaningful antitumor activity in heavily pretreated female patients with ER+, HER2– BC."

Clinical • Metastases • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Trial completion date: Mar 2024 ➔ Aug 2024

Combination therapy • Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Phase classification: P1b ➔ P1

Combination therapy • Metastases • Phase classification • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Active, not recruiting ➔ Completed

Metastases • Trial completion • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase I study of H3B-6545 in patients (pts) with estrogen receptor-positive (ER+) breast cancer (ESMO Asia 2023) - P1 | "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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: 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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | N=151 ➔ 206

Enrollment change • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Inc. | Trial completion date: Dec 2022 ➔ Oct 2023 | Trial primary completion date: Dec 2022 ➔ Oct 2023

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: 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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: Eisai Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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) - P1b | "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 • Combination therapy • P1 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: H3 Biomedicine Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. (PubMed, Mol Cancer Ther) - P1, P1/2, P1b | "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."

Journal • Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

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 | Sponsor: 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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: H3 Biomedicine Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

[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) - P1/2 | "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 • Anemia • Breast Cancer • Cardiovascular • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Sponsor: 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 • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2