Breast NeoplasmsPhase 1/2NCT03250676
Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer
A Phase 1/2 study testing H3B-6545 in people with Breast Neoplasms and Breast Cancer, run by Eisai Inc. at 39 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms, Breast Cancer, Estrogen-receptor Positive Breast Cancer
- What is being tested?
- H3B-6545
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 39 sitesin 3 countries
- Study dates
- 23 Aug 2017to 26 Oct 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
39 sites in 3 countries.
39 sites in 3 countries
United States23 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado - Cancer Center
Aurora, Colorado, 80045
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of North Carolina
Chapel Hill, North Carolina, 27599
Parkland Health and Hospital System
Dallas, Texas, 75235
UT Southwestern Medical Center
Dallas, Texas, 75390
Holy Cross Hospital Inc
Fort Lauderdale, Florida, 33308
Florida Cancer Specialists South
Fort Myers, Florida, 33901
Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix
Goodyear, Arizona, 85338
Saint Luke's Cancer Institute
Kansas City, Missouri, 64111
Research Medical Center
Kansas City, Missouri, 64132
Comprehensive Cancer Center of Nevada
Las Vegas, Nevada, 89169
University of California Los Angeles
Los Angeles, California, 90404
Tennessee Oncology
Nashville, Tennessee, 37203
Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta
Newnan, Georgia, 30265
Huntsman Cancer Institute at The University of Utah
Salt Lake City, Utah, 84112
University of California San Francisco
San Francisco, California, 94158
Florida Cancer Specialists and Research Institute
Sarasota, Florida, 34232
Florida Cancer Specialists North
St. Petersburg, Florida, 33705
Tyler Oncology/Oncology PA
Tyler, Texas, 75701
Carle Cancer Center
Urbana, Illinois, 61801
Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago
Zion, Illinois, 60099
France10 sites
Edog - Ico - Ppds
Angers, 49055
Hopital Jean Minjoz
Besançon, 25030
Centre Jean Perrin
Clermont-Ferrand, 63011
Centre Oscar Lambret
Lille, 59000
Hôpital Saint Louis
Paris, 75010
Hôpital de la Pitié Salpétrière
Paris, 75013
EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
Rennes, 35042
EDOG Institut de Cancerologie de l'Ouest - PPDS
Saint-Herblain, 44805
Institut de Cancérologie Strasbourg Europe
Strasbourg, 67200
Institut Gustave Roussy
Villejuif, 94805
United Kingdom6 sites
Velindre Cancer Centre
Cardiff, CF14 2TL
The Royal Marsden NHS Foundation Trust
Chelsea, London, SW3 6JJ
Barts Health NHS Trust
London, EC1A 7BE
Sarah Cannon Research Institute
London, W1G 6AD
Christie Hospital
Manchester, M20 4BX
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
About this study
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
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).
- Conditions
- Breast Neoplasms, Breast Cancer, Estrogen-receptor Positive Breast Cancer, Cancer, Breast, Breast Cancer Female, Breast Adenocarcinoma
- Being tested
- H3B-6545
- Keywords
- estrogen receptor, H3B-6545, breast cancer, Endocrine Therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
H3B-6545Drug
Oral capsules by mouth once daily
| Study group | Role | What they receive |
|---|---|---|
| H3B-6545 Arm 1: Dose escalation | Experimental | Not described Receives: Drug: H3B-6545 |
| H3B-6545 Arm 2: Phase 2 | Experimental | Not described Receives: Drug: H3B-6545 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting >72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting >24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting >7 days; Grade 4 or Grade 3 or intolerable Grade 2 toxicities of any non-hematologic adverse event.
Measured: Cycle 1 (Cycle length=28 days)
Phase 1 and Phase 2: Objective Response Rate (ORR)
ORR was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as defined by the Investigator based on radiologic criteria. ORR was defined as the percentage of participants who achieved a best overall response of confirmed partial response (PR) or complete response (CR). CR was defined as disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to less than (<)10 millimeter (mm). PR was defined as at least a 30 percentage (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg dose was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of progressive disease (PD) or death, whichever occurred first (up to 33 months)
Phase 1 and Phase 2: Duration of Response (DoR)
The DoR was assessed according to RECIST version 1.1. DoR was defined as the time from the date of the first documented CR/PR until the first documentation of disease progression or death, whichever comes first. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
Phase 1 and Phase 2: Disease Control Rate (DCR)
The DCR was assessed according to RECIST version 1.1. DCR was defined as the percentage of participants who achieved best response of CR, PR, or stable disease (SD). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
Phase 1 and Phase 2: Clinical Benefit Rate (CBR)
The CBR was assessed according to RECIST version 1.1. CBR defined as the percentage of participants with best overall response (BOR) of PR, CR, or durable SD (duration >=23 weeks). It was calculated for participants whose BOR was SD. CR defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
Phase 1 and Phase 2: Progression-free Survival (PFS)
PFS was defined as the time from the first dose date to the date of the first documentation of PD or death whichever occurred first. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
Phase 1 and Phase 2: Overall Survival (OS)
OS was defined as the time from first dose date to the date of death (event) or date last known alive (censored). As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Measured: Phase 1 and Phase 2: From the first dose of study drug to date of death or last known alive (up to 63 months)
Secondary outcomes (13)
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE was defined per NCI CTCAE version 4.03 as an adverse event (AE) with an onset that occurred after receiving study drug. An AE was defined as any untoward medical occurrence in a participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Pooled data from phase 1 and phase 2 was presented for 450 mg arm as enrolled participants in both the phases had similar demographics and disease characteristics with no major changes in inclusion/exclusion criteria as defined in the protocol.
Measured: From start of the study up to 74 months
Phase 1: (AUC0-t): Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point of H3B-6545
AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 time to last measurable point for H3B-6545.
Measured: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Cmax: Maximum Observed Plasma Concentration for H3B-6545
Cmax was defined as the maximum plasma concentration for H3B-6545.
Measured: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Tmax: Time of Maximum Observed Plasma Concentration of H3B-6545
Tmax was defined as the time to reach maximum observed plasma concentration for H3B-6545.
Measured: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Rac (Cmax): Accumulation Ratio of Cmax for H3B-6545
Accumulation ratio of Cmax was calculated as Cmax at Cycle 1 Day 15/Cmax at Cycle 1 Day 1.
Measured: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Rac (AUC0-24h): Accumulation Ratio of Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24h) for H3B-6545
Rac (AUC0-24h) was calculated as AUC(0-24h) at Cycle 1 Day 15/AUC(0-24h) at Cycle 1 Day 1.
Measured: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using AUC(0-24h)
Relative bioavailability based on food effect was calculated by taking ratio of AUC(0-24h) under fed condition divided by AUC(0-24h) under fasting condition. Data for the fasted and fed cohorts was collected on both Day 15 and Day 22 and was averaged.
Measured: Cycle 1 Days 15 and 22: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using Cmax
Relative bioavailability based on food effect was calculated by taking ratio of Cmax under fed condition divided by Cmax under fasting condition. Data for the fasted and fed cohorts was collected on both Day 15 and Day 22 and was averaged.
Measured: Cycle 1 Days 15 and 22: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Mean Change From Baseline in Endometrial Thickness Due to H3B-6545
Participants with an intact uterus underwent transvaginal ultrasound to examine the effect of H3B-6545 on endometrial thickness. Baseline was defined as the last non-missing value before the first dose of study drug (Day 1). Mean change from baseline was calculated as post-baseline visit value minus baseline value.
Measured: Baseline, Week 12, Week 36 and Week 60
Phase 2: Mean Change From Baseline in Uterine Volume Due to H3B-6545
Participants with an intact uterus underwent transvaginal ultrasound to examine the effect of H3B-6545 on uterine volume. Baseline was defined as the last non-missing value before the first dose of study drug (Day 1). Mean change from baseline was calculated as post-baseline visit value minus baseline value.
Measured: Baseline, Week 12 and Week 36
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Bone-specific Alkaline Phosphatase
Blood samples were collected at indicated timepoint for evaluation of bone turn-over marker BSAP. Baseline is defined as the last non-missing value before the first dose of study drug (Day1). Change from baseline was calculated as post-baseline visit value minus baseline value. Pooled data from phase 1 and phase 2 was presented for 450 mg arm as enrolled participants in both the phases had similar demographics and disease characteristics with no major changes in inclusion/exclusion criteria as defined in the protocol.
Measured: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Amino-Terminal Propeptide of Type 1 Collagen (PINP)
Blood samples were collected at indicated timepoint for evaluation of Bone turn-over marker PINP. Baseline is defined as the last non-missing value before the first dose of study drug (Day 1). Change from baseline was calculated as post-baseline visit value minus baseline value. Pooled data from phase 1 and phase 2 was presented for 450 mg arm as enrolled participants in both the phases had similar demographics and disease characteristics with no major changes in inclusion/exclusion criteria as defined in the protocol.
Measured: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
Blood samples were collected at indicated timepoint for evaluation of Bone turn-over marker CTX. Baseline is defined as the last non-missing value before the first dose of study drug (Day 1). Change from baseline was calculated as post-baseline visit value minus baseline value. Pooled data from phase 1 and phase 2 was presented for 450 mg arm as enrolled participants in both the phases had similar demographics and disease characteristics with no major changes in inclusion/exclusion criteria as defined in the protocol.
Measured: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start23 Aug 2017
- Primary completion26 Oct 2023
- Study completion26 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03250676
- Sponsor's protocol ID
- H3B-6545-A001-101
- Other IDs
- 2018-000570-29, 2018
- Status last verified
- Mar 2024
- First submitted
- 11 Aug 2017
- Last updated
- 25 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hamilton E, Pluard T, Wang JS, Morikawa A, Johnston S, Dees EC, Vaklavas C, Armstrong A, Munster P, Unni N, Wright GS, Kayali F, Song T, Rong Y, Yamaguchi K, Juric D. Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer Res. 2025 Aug 19;27(1):151. doi: 10.1186/s13058-025-02069-8.
PubMed 40830892Furman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378.
PubMed 35642432
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03250676
- Acronym / sponsor ID
- H3B-6545-A001-101
- Conditions
- Breast Neoplasms, Breast Cancer, Estrogen-receptor Positive Breast Cancer, Cancer, Breast, Breast Cancer Female, Breast Adenocarcinoma
- Keywords
- estrogen receptor, H3B-6545, breast cancer, Endocrine Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Aug 2017 (actual)
- Primary completion
- 26 Oct 2023 (actual)
- Study completion
- 26 Oct 2023 (actual)
- First posted
- 16 Aug 2017 (actual)
- Results
- Posted 25 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H3B-6545 Arm 1: Dose escalation | Experimental | Drug: H3B-6545 |
| H3B-6545 Arm 2: Phase 2 | Experimental | Drug: H3B-6545 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| H3B-6545Oral capsules by mouth once daily | Drug | H3B-6545 Arm 1: Dose escalation, H3B-6545 Arm 2: Phase 2 |
Primary outcome
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (Cycle length=28 days)
DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting >72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting >24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting >7 days; Grade 4 or Grade 3 or intolerable Grade 2 toxicities of any non-hematologic adverse event.
Phase 1 and Phase 2: Objective Response Rate (ORR)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of progressive disease (PD) or death, whichever occurred first (up to 33 months)
ORR was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as defined by the Investigator based on radiologic criteria. ORR was defined as the percentage of participants who achieved a best overall response of confirmed partial response (PR) or complete response (CR). CR was defined as disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to less than (<)10 millimeter (mm). PR was defined as at least a 30 percentage (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg dose was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Phase 1 and Phase 2: Duration of Response (DoR)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
The DoR was assessed according to RECIST version 1.1. DoR was defined as the time from the date of the first documented CR/PR until the first documentation of disease progression or death, whichever comes first. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Phase 1 and Phase 2: Disease Control Rate (DCR)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
The DCR was assessed according to RECIST version 1.1. DCR was defined as the percentage of participants who achieved best response of CR, PR, or stable disease (SD). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Phase 1 and Phase 2: Clinical Benefit Rate (CBR)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
The CBR was assessed according to RECIST version 1.1. CBR defined as the percentage of participants with best overall response (BOR) of PR, CR, or durable SD (duration >=23 weeks). It was calculated for participants whose BOR was SD. CR defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Phase 1 and Phase 2: Progression-free Survival (PFS)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 33 months)
PFS was defined as the time from the first dose date to the date of the first documentation of PD or death whichever occurred first. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study. As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
Phase 1 and Phase 2: Overall Survival (OS)
Time frame: Phase 1 and Phase 2: From the first dose of study drug to date of death or last known alive (up to 63 months)
OS was defined as the time from first dose date to the date of death (event) or date last known alive (censored). As per planned analysis, pooled data for phase 1 and phase 2 for 450 mg arm was presented as enrolled participants in both the phases had similar demographics and disease characteristics.
13 secondary outcomes
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From start of the study up to 74 months
Phase 1: (AUC0-t): Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point of H3B-6545
Time frame: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Cmax: Maximum Observed Plasma Concentration for H3B-6545
Time frame: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Tmax: Time of Maximum Observed Plasma Concentration of H3B-6545
Time frame: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Rac (Cmax): Accumulation Ratio of Cmax for H3B-6545
Time frame: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 1: Rac (AUC0-24h): Accumulation Ratio of Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24h) for H3B-6545
Time frame: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using AUC(0-24h)
Time frame: Cycle 1 Days 15 and 22: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using Cmax
Time frame: Cycle 1 Days 15 and 22: predose and up to 24 hours postdose (Cycle length = 28 days)
Phase 2: Mean Change From Baseline in Endometrial Thickness Due to H3B-6545
Time frame: Baseline, Week 12, Week 36 and Week 60
Phase 2: Mean Change From Baseline in Uterine Volume Due to H3B-6545
Time frame: Baseline, Week 12 and Week 36
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Bone-specific Alkaline Phosphatase
Time frame: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Amino-Terminal Propeptide of Type 1 Collagen (PINP)
Time frame: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
Time frame: Baseline (predose), Cycle 2 Day 15, Cycle 4 Day 1, and off-Treatment (up to 33 months) (Cycle length = 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40830892Hamilton E, Pluard T, Wang JS, Morikawa A, Johnston S, Dees EC, Vaklavas C, Armstrong A, Munster P, Unni N, Wright GS, Kayali F, Song T, Rong Y, Yamaguchi K, Juric D. Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer Res. 2025 Aug 19;27(1):151. doi: 10.1186/s13058-025-02069-8.
- Derived from this study: PubMed 35642432Furman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378.
Related trials for Breast Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
39 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing H3B-6545 in people with Breast Neoplasms and Breast Cancer, run by Eisai Inc. at 39 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (Cycle length=28 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03250676, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.