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

Inclusion criteria

• 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).
• Serum albumin >=3.0 g/dL (>=30 gram per liter [g/L]).
• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) <=3.0*ULN. If the participant has liver metastases, ALT and AST <=5.0*ULN.
• Total serum bilirubin less than (<) 1.5*ULN.
• Participants who are expected to survive for 3 months or longer after starting administration of the investigational drug.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion criteria

• 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.
• Heart Rate <60 beats per minute (bpm) on the screening.
• On screening, any of the following cardiac parameters: PR interval >220 millisecond (msec), QRS interval >10˄9 msec, or QT interval with Fridericia's correction (QTcF) >450 msec.
• Systolic blood pressure (BP) not deemed clinically controlled by the investigator.
• Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of H3B-6545.
• Participant has a known hypersensitivity to any of the excipients of H3B-6545.
• Known to be human immunodeficiency virus (HIV) positive.
• Active viral hepatitis (B or C) as demonstrated by positive serology. Participants with chronic hepatitis B virus (HBV) infection is on antiviral therapy is eligible.
• Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate participant participation in the clinical study (example- chronic pancreatitis, thyroid dysfunction etc).
• Any adverse event related to previous therapies for breast cancer that has not resolved to <=Grade 1 (with exception of the alopecia).
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG] test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• Women of childbearing potential who don't agree that both the participant and her partner will use a medically effective method for contraception (as below) throughout the entire study period or for 28 days after study drug discontinuation.

Note: Condom*, contraceptive sponge**, foam**, jelly**, diaphragm**, intrauterine device (IUD) *, or use of oral contraception* from at least 4 weeks before starting the study treatment (*Approved drugs or certified medical devices in Japan, **Non-approved drugs or certified medical devices in Japan) If a participant is on oral contraceptives, they should also be using some additional method.

• Alcohol dependency within 6 months before study entry.
• Participant has a concurrent malignancy or malignancy within 3 years of enrollment, with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• Diagnosed with meningeal carcinomatosis.
• Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example- radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
• Participant has a known intolerability to any oral antihistamine drug (only for Antihistamine Prophylactic Administration Part and Randomization Part).
• Participant needs to receive systemic or topical usage of either antihistamine or corticosteroid during Cycle 1 (only for Randomization Part).

Note: The following uses of corticosteroids are permitted: inhaled sprays (example, for obstructive airways diseases), eye drops or local injections (example, intra-articular).

• Participants initiated to receive drugs may cause rash 7 days prior to starting study drug.