Clinical Trial - NCT03250676

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

Recruiting

Sponsor: H3 Biomedicine Inc.

Collaborators: Eisai Inc.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03250676

Protocol Info

Short Description: 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
Long Description: A Phase I-II 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
MGH Status: Open
Sponsor: H3 Biomedicine Inc.
Disease Program: Breast

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

The purpose of phase 1 is to determine safety, tolerability and pharmacokinetics (PK) of H3B-6545 in women with locally advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer. The purpose of phase 2 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 Title Intervention Phase
Breast Neoplasms Breast Cancer Estrogen-receptor Positive Breast Cancer Cancer, Breast Breast Cancer Female Breast Adenocarcinoma Estrogen Receptor Positive Tumor ER Positive H3B-6545 Phase 1/Phase 2
Study Type Interventional
Official Title A Phase I-II 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

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs) [Time Frame: Phase 1 Cycle 1 (28 days)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]


Secondary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Objective Response Rate (ORR) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Duration of Response (DoR) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Disease Control Rate (DCR) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Clinical Benefit Rate (CBR) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Progression-free survival (PFS) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: Phase 1 and 2 up to approximately 36 months] [Designated as safety issue: ]

Estimated Enrollment: 148
Study Start Date: August 2017
Estimated Study Completion Date: January 2024
Estimated Primary Completion Date: January 2022
Arms Assigned Interventions

Experimental:H3B-6545 Arm 1: Dose escalation

Drug:H3B-6545
Oral capsules by mouth once daily

Experimental:H3B-6545 Arm 2: Phase 2

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: Female

Accepts Healthly Volunteers: No

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 must have received prior cyclin-dependent kinase (CDK4/6) inhibitor therapy.

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 must have measurable disease at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

8. Participants under amendment 6 must have ESR1 Y537S mutation in absence of ESR1 D538G mutation as per the results of a central laboratory.

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT03250676

Locations

  • United States, California
    • University of California Los Angeles Los Angeles, California, United States, 90404
    • University of California San Francisco San Francisco, California, United States, 94158
  • United States, Florida
    • Holy Cross Hospital Inc Fort Lauderdale, Florida, United States, 33308
    • Florida Cancer Specialists South Fort Myers, Florida, United States, 33901
    • Florida Cancer Specialists North Saint Petersburg, Florida, United States, 33705
    • Florida Cancer Specialists and Research Institute Sarasota, Florida, United States, 34232
  • United States, Illinois
    • Carle Cancer Center Urbana, Illinois, United States, 61801
  • United States, Maryland
    • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, Maryland, United States, 21287
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
  • United States, Missouri
    • Saint Luke's Cancer Institute Kansas City, Missouri, United States, 64111
    • Research Medical Center Kansas City, Missouri, United States, 64132
  • United States, North Carolina
    • University of North Carolina Chapel Hill, North Carolina, United States, 27599
  • United States, Tennessee
    • Tennessee Oncology Nashville, Tennessee, United States, 37203
  • United States, Texas
    • UT Southwestern Medical Center Dallas, Texas, United States, 75390
  • United States, Utah
    • Huntsman Cancer Institute at The University of Utah Salt Lake City, Utah, United States, 84112
  • United Kingdom,
    • Velindre Cancer Centre Cardiff, , United Kingdom, CF14 2TL
    • Barts Health NHS Trust London, , United Kingdom, EC1A 7BE
    • Christie Hospital Manchester, , United Kingdom, M20 4BX
    • The Royal Marsden NHS Foundation Trust Sutton, , United Kingdom, SM2 5PT

Sponsors and Collaborators

H3 Biomedicine Inc.

Eisai Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03250676
Other Study ID Numbers: 2018-000570-29
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Eisai Inc.:

estrogen receptor

H3B-6545

breast cancer

Endocrine Therapy

Additional relevant MeSH terms:

Breast Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on April 29, 2021