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

December 22, 2023 updated by: Eisai Inc.

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

206

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49055
        • Edog - Ico - Ppds
      • Besançon, France, 25030
        • Hôpital Jean Minjoz
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Lille, France, 59000
        • Centre Oscar Lambret
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75013
        • Hopital de la Pitie Salpetriere
      • Rennes, France, 35042
        • EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
      • St. Herblain, France, 44805
        • EDOG Institut de Cancerologie de l'Ouest - PPDS
      • Strasbourg, France, 67200
        • Institut de cancerologie Strasbourg Europe
      • Villejuif Cedex, France, 94805
        • Institut Gustave Roussy
  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • London, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute
      • Manchester, United Kingdom, M20 4BX
        • Christie Hospital
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
    • London
      • Chelsea, London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust
  • United States
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix
    • California
      • Los Angeles, California, United States, 90404
        • University of California Los Angeles
      • San Francisco, California, United States, 94158
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado - Cancer Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital Inc
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists South
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists NORTH
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists and Research Institute
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta
    • Illinois
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Zion, Illinois, United States, 60099
        • Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Cancer Institute
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Center of Nevada
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Dallas, Texas, United States, 75235
        • Parkland Health and Hospital System
      • Tyler, Texas, United States, 75701
        • Tyler Oncology/Oncology PA
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute at The University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: Phase 1 Cycle 1 (28 days)
Phase 1 Cycle 1 (28 days)
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)
Phase 1 and 2 continuously throughout the study until 28 days after treatment discontinuation (up to 36 months)

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
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
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
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
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
Objective Response Rate (ORR)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months
Duration of Response (DoR)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months
Disease Control Rate (DCR)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months
Clinical Benefit Rate (CBR)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months
Progression-free survival (PFS)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months
Overall Survival (OS)
Time Frame: Phase 1 and 2 up to approximately 36 months
Phase 1 and 2 up to approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eisai Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2017

Primary Completion (Actual)

October 26, 2023

Study Completion (Actual)

October 26, 2023

Study Registration Dates

First Submitted

August 11, 2017

First Submitted That Met QC Criteria

August 11, 2017

First Posted (Actual)

August 16, 2017

Study Record Updates

Last Update Posted (Actual)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H3B-6545-A001-101
  • 2018-000570-29 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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