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

• Sponsor: H3 Biomedicine Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03250676
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 151
• Locations: 39
• Arms: 2
• Anticipated Duration (Months): 64.5
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

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).

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

• Study Type: Interventional
• Actual Enrollment: 151 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: Aug 17, 2017
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

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

Primary Outcome Measures

1. Number of Participants with Dose-limiting Toxicities (DLTs) [Phase 1 Cycle 1 (28 days)]

2. 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 Outcome Measures

1. 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]

2. 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]

3. 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]

4. Objective Response Rate (ORR) [Phase 1 and 2 up to approximately 36 months]

5. Duration of Response (DoR) [Phase 1 and 2 up to approximately 36 months]

6. Disease Control Rate (DCR) [Phase 1 and 2 up to approximately 36 months]

7. Clinical Benefit Rate (CBR) [Phase 1 and 2 up to approximately 36 months]

8. Progression-free survival (PFS) [Phase 1 and 2 up to approximately 36 months]

9. Overall Survival (OS) [Phase 1 and 2 up to approximately 36 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy 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 (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

Locations

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

Sponsors and Collaborators

• H3 Biomedicine Inc.
• Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: H3 Biomedicine Inc.
• ClinicalTrials.gov Identifier: NCT03250676
• Other Study ID Numbers: H3B-6545-A001-101; 2018-000570-29
• First Posted: Aug 16, 2017
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by H3 Biomedicine Inc.: estrogen receptor; H3B-6545; breast cancer; Endocrine Therapy
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

No Results Posted as of Jun 30, 2022