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

Primary Purpose

Breast Neoplasms, Breast Cancer, Estrogen-receptor Positive Breast Cancer

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

H3B-6545

About this trial

This is an interventional treatment trial for Breast Neoplasms focused on measuring estrogen receptor, H3B-6545, breast cancer, Endocrine Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Pre- or post-menopausal women.
ER-positive, HER2-negative breast cancer that is advanced or metastatic.
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.
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.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Adequate bone marrow and organ function.
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.
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:

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

Sites / Locations

Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix
University of California Los Angeles
University of California San Francisco
University of Colorado - Cancer Center
Holy Cross Hospital Inc
Florida Cancer Specialists South
Florida Cancer Specialists North
Florida Cancer Specialists and Research Institute
Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta
Carle Cancer Center
Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Massachusetts General Hospital
University of Michigan
Saint Luke's Cancer Institute
Research Medical Center
Comprehensive Cancer Center of Nevada
University of North Carolina
Tennessee Oncology
Parkland Health and Hospital System
UT Southwestern Medical Center
Tyler Oncology/Oncology PA
Huntsman Cancer Institute at The University of Utah
Edog - Ico - Ppds
Hopital Jean Minjoz
Centre Jean Perrin
Centre Oscar Lambret
Hôpital Saint Louis
Hôpital de la Pitié Salpétrière
EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
EDOG Institut de Cancerologie de l'Ouest - PPDS
Institut de Cancérologie Strasbourg Europe
Institut Gustave Roussy
The Royal Marsden NHS Foundation Trust
Velindre Cancer Centre
Barts Health NHS Trust
Sarah Cannon Research Institute
Christie Hospital
The Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

H3B-6545 Arm 1: Dose escalation

H3B-6545 Arm 2: Phase 2

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs)

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

Secondary Outcome Measures

Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6545

Mean Maximum Observed Plasma Concentration (Cmax) of H3B-6545

Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545

Objective Response Rate (ORR)

Duration of Response (DoR)

Disease Control Rate (DCR)

Clinical Benefit Rate (CBR)

Progression-free survival (PFS)

Overall Survival (OS)

Full Information

NCT ID

NCT03250676

First Posted

August 11, 2017

Last Updated

March 22, 2023

Sponsor

Eisai Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03250676

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 17, 2017 (Actual)

Primary Completion Date

October 1, 2023 (Anticipated)

Study Completion Date

October 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

estrogen receptor, H3B-6545, breast cancer, Endocrine Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

206 (Actual)

8. Arms, Groups, and Interventions

Arm Title

H3B-6545 Arm 1: Dose escalation

Arm Type

Experimental

Arm Title

H3B-6545 Arm 2: Phase 2

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

H3B-6545

Intervention Description

Oral capsules by mouth once daily

Primary Outcome Measure Information:

Title

Number of Participants with Dose-limiting Toxicities (DLTs)

Time Frame

Phase 1 Cycle 1 (28 days)

Title

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 Measure Information:

Title

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

Title

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

Title

Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545

Time Frame

Title

Objective Response Rate (ORR)

Time Frame