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

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ClinicalTrials.gov Identifier: NCT03250676
Recruitment Status : Completed
First Posted : August 16, 2017
Last Update Posted : December 26, 2023
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Study Description
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Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Breast Neoplasms Breast Cancer Estrogen-receptor Positive Breast Cancer Cancer, Breast Breast Cancer Female Breast Adenocarcinoma Estrogen Receptor Positive Tumor ER Positive Drug: H3B-6545 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 206 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2 Multicenter, Open Label Trial of H3B-6545, a Covalent Antagonist of Estrogen Receptor Alpha, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer
Actual Study Start Date : August 17, 2017
Actual Primary Completion Date : October 26, 2023
Actual Study Completion Date : October 26, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Estrogens

Arms and Interventions
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Arm Intervention/treatment
Experimental: H3B-6545 Arm 1: Dose escalation Drug: H3B-6545
Oral capsules by mouth once daily
Experimental: H3B-6545 Arm 2: Phase 2 Drug: H3B-6545
Oral capsules by mouth once daily


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Phase 1 Cycle 1 (28 days) ]
  2. Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Phase 1 and 2 continuously throughout the study until 28 days after treatment discontinuation (up to 36 months) ]

Secondary Outcome Measures :
  1. Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6545 [ Time Frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose ]
  2. Mean Maximum Observed Plasma Concentration (Cmax) of H3B-6545 [ Time Frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 (pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose ]
  3. Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545 [ Time Frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose ]
  4. Objective Response Rate (ORR) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]
  5. Duration of Response (DoR) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]
  6. Disease Control Rate (DCR) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]
  7. Clinical Benefit Rate (CBR) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]
  8. Progression-free survival (PFS) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]
  9. Overall Survival (OS) [ Time Frame: Phase 1 and 2 up to approximately 36 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03250676


Locations
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Sponsors and Collaborators
Eisai Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03250676    
Other Study ID Numbers: H3B-6545-A001-101
2018-000570-29 ( EudraCT Number )
First Posted: August 16, 2017    Key Record Dates
Last Update Posted: December 26, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
estrogen receptor
H3B-6545
breast cancer
Endocrine Therapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases