Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer

Eisai

Status and phase: Completed; Phase 2; Phase 1

Conditions: Estrogen-receptor Positive Breast Cancer; ER Positive; Breast Cancer; Breast Cancer Female; Cancer, Breast; Breast Adenocarcinoma; Breast Neoplasms; Estrogen Receptor Positive Tumor

Treatments: Drug: H3B-6545

Study type: Interventional

Funder types: Industry

Identifiers

NCT03250676

H3B-6545-A001-101

2018-000570-29 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of phase 1 portion of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of H3B-6545 in women with locally advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer.

The primary purpose of phase 2 portion of this study is to estimate the efficacy of H3B-6545 in terms of best overall response rate, duration of response (DoR), clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in all participants with ER-positive, HER2-negative breast cancer and in those with and without ER alpha mutation (including a clonal estrogen receptor 1 gene [ESR1] Y537S mutation).

Enrollment: 151 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Pre- or post-menopausal women.
2. ER-positive, HER2-negative breast cancer that is advanced or metastatic.
3. Progressed on prior therapy. Multiple prior lines of therapy allowed in Phase 1 and 2. Participants under amendment 6 (or subsequent amendments) must have received prior cyclin-dependent kinase (CDK4/6) inhibitor therapy. Up to one prior chemotherapy in the metastatic setting is allowed.
4. A recent archival tumor tissue obtained within 6 months prior to enrollment or a fresh tumor biopsy must be provided. A second biopsy after initiating trial therapy is not required.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. Adequate bone marrow and organ function.
7. Participants under amendment 6 (or subsequent amendments) must have measurable disease at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
8. Participants under amendment 6 (or subsequent amendments) must have ESR1 Y537S mutation in absence of ESR1 D538G mutation as per the results of a central laboratory from a Nucleic Acids Whole Blood sample.

Exclusion criteria

1. Participants must have at least one measurable lesion.
2. Participant with inflammatory breast cancer.
3. Participant has received more than one prior chemotherapy regimen for metastatic disease (Phase 2 only).
4. Females of childbearing potential who are unable or unwilling to follow adequate contraceptive measures.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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151 participants in 2 patient groups

H3B-6545 Arm 1: Dose escalation

Experimental group

Treatment:

Drug: H3B-6545

H3B-6545 Arm 2: Phase 2

Experimental group

Treatment:

Drug: H3B-6545