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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03250676
• Other study ID #: H3B-6545-A001-101
• Secondary ID: 2018-000570-29
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 17, 2017
• Est. completion date: October 26, 2023

Study information

• Verified date: March 2023
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: October 26, 2023
• Est. primary completion date: October 26, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• H3B-6545
Oral capsules by mouth once daily

Locations

Country	Name	City	State
France	Edog - Ico - Ppds	Angers
France	Hopital Jean Minjoz	Besançon
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Oscar Lambret	Lille
France	Hôpital de la Pitié Salpétrière	Paris
France	Hôpital Saint Louis	Paris
France	EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS	Rennes
France	EDOG Institut de Cancerologie de l'Ouest - PPDS	St. Herblain
France	Institut de Cancérologie Strasbourg Europe	Strasbourg
France	Institut Gustave Roussy	Villejuif Cedex
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	The Royal Marsden NHS Foundation Trust	Chelsea	London
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado - Cancer Center	Aurora	Colorado
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Parkland Health and Hospital System	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Holy Cross Hospital Inc	Fort Lauderdale	Florida
United States	Florida Cancer Specialists South	Fort Myers	Florida
United States	Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix	Goodyear	Arizona
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Comprehensive Cancer Center of Nevada	Las Vegas	Nevada
United States	University of California Los Angeles	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta	Newnan	Georgia
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	Huntsman Cancer Institute at The University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Florida Cancer Specialists and Research Institute	Sarasota	Florida
United States	Tyler Oncology/Oncology PA	Tyler	Texas
United States	Carle Cancer Center	Urbana	Illinois
United States	Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Countries where clinical trial is conducted

United States,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose-limiting Toxicities (DLTs)		Phase 1 Cycle 1 (28 days)
Primary	Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Phase 1 and 2 continuously throughout the study until 28 days after treatment discontinuation (up to 36 months)
Secondary	Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6545		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
Secondary	Mean Maximum Observed Plasma Concentration (Cmax) of H3B-6545		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
Secondary	Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545		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
Secondary	Objective Response Rate (ORR)		Phase 1 and 2 up to approximately 36 months
Secondary	Duration of Response (DoR)		Phase 1 and 2 up to approximately 36 months
Secondary	Disease Control Rate (DCR)		Phase 1 and 2 up to approximately 36 months
Secondary	Clinical Benefit Rate (CBR)		Phase 1 and 2 up to approximately 36 months
Secondary	Progression-free survival (PFS)		Phase 1 and 2 up to approximately 36 months
Secondary	Overall Survival (OS)		Phase 1 and 2 up to approximately 36 months