Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

NCT04568902 | Completed Phase 1

• 1 other identifier: H3B-6545-J081-103
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of study is to determine tolerability and safety profile of H3B-6545 in Japanese women with ER-positive, HER2-negative breast cancer, and also to confirm the dose applicability to Japanese.

Conditions

Breast Neoplasms

Keywords

H3B-6545; ER-positive; HER2-negative

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  Toxicity will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), v5.0. DLT is defined as any of the following events occurred within the Cycle 1 of the administration of H3B-6545: Febrile neutropenia, Grade 4 neutropenia that does not resolve to Grade\<=2 within 7days, Grade 4 thrombocytopenia, Grade3 thrombocytopenia\>=7days or requiring platelet transfusion, Grade3 thrombocytopenia associated with bleeding, Grade4 anemia or Grade3 anemia requiring erythrocyte transfusion; Grade3 or 4 bilirubin increase, AST or ALT\>=10\*ULN which does not resolve to Grade2 or less within 7days and/or else is clinically significant; Non-hematological toxicities Grade4 and Grade3 with exception of abnormal clinical laboratory values with no clinical significance and events which can be managed and controlled to Grade2 or less by maximal medical management within 7days, participant administered\<70% of prescribed dose due to intolerable toxicity.

  Up to Cycle 1 (each cycle length is equal to [=] 28 days)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Baseline up to 36 months

• Percentage of Participants With Incidence of Rash

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in Laboratory Values

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in Weight Values

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in Physical Examinations

  Baseline up to 36 months

• Number of Participants With Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)

  ECOG performance score is measured on 6 point scale to assess participant's performance status, where: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead.

  Baseline up to 36 months

Secondary Outcomes (8)

• Cmax: Maximum Observed Plasma Concentration of H3B-6545

  Dose Escalation and Antihistamine Prophylactic Administration Part: Cycle 1 Days 1 and 15: 0-24 hours post dose; Randomization Part: Cycle 1 Days 1 and 15: 0-6 hours post dose (cycle length=28 days)

• Tmax: Time of Maximum Observed Plasma Concentration of H3B-6545

  Dose Escalation and Antihistamine Prophylactic Administration Part: Cycle 1 Days 1 and 15: 0-24 hours post dose; Randomization Part: Cycle 1 Days 1 and 15: 0-6 hours post dose (cycle length=28 days)

• AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of H3B-6545

  Dose Escalation and Antihistamine Prophylactic Administration Part: Cycle 1 Days 1 and 15: 0-24 hours post dose; Randomization Part: Cycle 1 Days 1 and 15: 0-6 hours post dose (cycle length=28 days)

• Rac: Accumulation Ratio of H3B-6545

  Dose Escalation and Antihistamine Prophylactic Administration Part: Cycle 1 Days 1 and 15: 0-24 hours post dose; Randomization Part: Cycle 1 Days 1 and 15: 0-6 hours post dose (cycle length=28 days)

• AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of H3B-6545

  Dose Escalation and Antihistamine Prophylactic Administration Part: Cycle 1 Days 1 and 15: 0-24 hours post dose; Randomization Part: Cycle 1 Days 1 and 15: 0-6 hours post dose (cycle length=28 days)

Study Arms (4)

Dose Escalation Part: H3B-6545 300 mg

EXPERIMENTAL

Participants will receive H3B-6545 300 milligram (mg) tablets, orally, once daily in 28 days cycle until disease progression, violation of study requirements, unable to continue study based on investigator opinion or withdrawal of consent.

Drug: H3B-6545

Dose Escalation Part: H3B-6545 450 mg

EXPERIMENTAL

Participants will receive H3B-6545 450 mg tablets, orally, once daily in 28 days cycle until disease progression, violation of study requirements, unable to continue study based on investigator opinion or withdrawal of consent.

Drug: H3B-6545

Antihistamine Prophylactic Administration Part

EXPERIMENTAL

Participants will receive prophylactic treatment with non-sedating systemic antihistamine, orally, once from Cycle 1 Day 1 until Cycle 1 Day 28, followed by H3B-6545 450 mg tablets, orally, once daily in 28 days cycle until disease progression, violation of study requirements, unable to continue study based on investigator opinion or withdrawal of consent.

Drug: H3B-6545; Drug: Antihistamine

Randomization Part

EXPERIMENTAL

Participants will be randomized in 1:1 ratio to receive H3B-6545 450 mg, tablets, orally, once daily in 28 days cycle either with non-sedating systemic antihistamine prophylactic administration from Day 1 until Day 28 of Cycle 1 OR without antihistamine prophylactic administration until disease progression, violation of study requirements, unable to continue study based on investigator opinion or withdrawal of consent.

Drug: H3B-6545; Drug: Antihistamine

Interventions

H3B-6545 DRUG

H3B-6545 oral tablets.

Antihistamine Prophylactic Administration Part; Dose Escalation Part: H3B-6545 300 mg; Dose Escalation Part: H3B-6545 450 mg; Randomization Part

Antihistamine DRUG

Systemic antihistamine oral drug such as fexofenadine, loratadine and cetirizine.

Antihistamine Prophylactic Administration Part; Randomization Part

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a histologically and/or cytologically confirmed diagnosis of ER-positive, HER2-negative breast cancer.
• Note: Status of ER and HER2 should be diagnosed by method approved by regulatory authority
• Only females, age greater than or equal to (\>=) 20 years at the time of informed consent.
• Prior therapy for breast cancer in the adjuvant and/or advanced/metastatic setting must have included a minimum of:
• two prior hormonal therapies, or
• one prior hormonal therapy and one prior chemotherapy regimen, or
• one prior hormonal therapy and a cyclin-dependent kinase (CDK4/6) inhibitor.
• Participant has an ECOG-PS of 0 or 1.
• Participant has adequate bone marrow and organ function, as defined by the following laboratory values:
• Absolute neutrophil count (ANC) \>=1.5\*10˄9/liter (L).
• Platelets \>=100\*10˄9/L.
• Hemoglobin \>=9.0 gram per deciliter (g/dL).
• Potassium, sodium, calcium (corrected for serum albumin) and magnesium less than or equal to (\<=) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
• International normalized ratio (INR) \<=1.5.
• Serum creatinine \<=1.5\*upper limit of normal (ULN).

You may not qualify if:

• Participant with inflammatory breast cancer.
• Participant is currently receiving or has received systemic corticosteroids \<=2 weeks prior to starting study drug, or has not fully recovered from side effects of such treatment.
• Note: The following uses of corticosteroids are permitted: inhaled sprays (example- for obstructive airways diseases), eye drops or local injections (example- intra-articular).
• Washout period required from the end of prior treatment to the first administration of study drug will be as follows.
• Anti-cancer therapy
• Antibody and other study drugs: greater than (\>) 4 weeks (however, in the case where the half-life of other study drugs is known and 5\*half-lives of that study drug is less than or equal to 4 weeks, participants can be eligible after \>=5\*half-lives of that study drug has passed).
• Prior chemotherapy (except small-molecule targeted therapy), surgical therapy, radiation therapy: \>3 weeks.
• Endocrine therapy, immunotherapy (except antibody drug), small-molecule targeted therapy: \>2 weeks.
• Supportive therapy • Blood/platelet transfusion, hematopoietic stimulating agent including granulocyte colony-stimulating factor (G-CSF) formulation: \>2 weeks.
• Participant has active cardiac disease or a history of cardiac dysfunction, including any of the following:
• History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry.
• History of documented congestive heart failure (New York Heart Association \[NYHA\] functional classification II to IV).
• Documented cardiomyopathy.
• Participant has a left ventricular ejection fraction (LVEF) \<50 percent (%) as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
• History of any cardiac arrhythmias, example- ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (2)

Eisai Trial Site 2

Chūōku, Japan

Location

Eisai Trial Site 1

Kōtoku, Japan

Location

Related Publications (1)

• Furman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378.

  PMID: 35642432 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

H3B-6545; Histamine Antagonists

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 29, 2020
• Study Start: September 30, 2020
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: October 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (2)