Phase 2
N=151
Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer
Breast Neoplasms · Breast Cancer · Estrogen-receptor Positive Breast Cancer · Cancer, Breast · Breast Cancer Female
Bottom Line
View on ClinicalTrials.gov: NCT03250676 ↗Enrolled (actual)
151
Serious AEs
23.8%
Results posted
Feb 2025
Primary outcome: Primary: Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- H3B-6545 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Eisai Inc.
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) |
0; 0; 0; 0; 2 | — |
| PRIMARY Phase 1 and Phase 2: Objective Response Rate (ORR) |
16.7; 9.1; 0; 20.2; 0 | — |
| PRIMARY Phase 1 and Phase 2: Duration of Response (DoR) |
7.95; 6.05; 9.23 | — |
| PRIMARY Phase 1 and Phase 2: Disease Control Rate (DCR) |
100.0; 54.5; 30.0; 61.7; 40.0 | — |
| PRIMARY Phase 1 and Phase 2: Clinical Benefit Rate (CBR) |
83.3; 27.3; 20.0; 41.5; 40.0 | — |
| PRIMARY Phase 1 and Phase 2: Progression-free Survival (PFS) |
9.28; 3.38; 1.84; 4.60; 2.76 | — |
| PRIMARY Phase 1 and Phase 2: Overall Survival (OS) |
12.37; 11.25; 13.50; 21.52; 5.32 | — |
| SECONDARY Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
6; 12; 11; 115; 7; 2 | — |
| SECONDARY Phase 1: (AUC0-t): Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point of H3B-6545 |
1680; 3310; 8520; 16200; 12600; 2590 | — |
| SECONDARY Phase 1: Cmax: Maximum Observed Plasma Concentration for H3B-6545 |
178; 391; 879; 1500; 1490; 287 | — |
| SECONDARY Phase 1: Tmax: Time of Maximum Observed Plasma Concentration of H3B-6545 |
3.05; 3.00; 3.97; 4.00; 4.00; 2.00 | — |
| SECONDARY Phase 1: Rac (Cmax): Accumulation Ratio of Cmax for H3B-6545 |
1.61; 1.52; 1.37; 1.05; 0.598 | — |
| SECONDARY 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 |
1.52; 1.55; 1.23; 0.917; 0.646 | — |
| SECONDARY Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using AUC(0-24h) |
1.53 | — |
| SECONDARY Phase 2: Relative Bioavailability (Food Effect) of H3B-6545 Assessed Using Cmax |
1.51 | — |
| SECONDARY Phase 2: Mean Change From Baseline in Endometrial Thickness Due to H3B-6545 |
4.079; 5.400; -0.050 | — |
| SECONDARY Phase 2: Mean Change From Baseline in Uterine Volume Due to H3B-6545 |
66.822; 41.083 | — |
| SECONDARY Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Bone-specific Alkaline Phosphatase |
-5.543; 2.327; 5.912; -5.683; -0.390; 0.381 | — |
| SECONDARY Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - Amino-Terminal Propeptide of Type 1 Collagen (PINP) |
-32.750; -14.139; 53.568; 26.242; 38.750; -35.500 | — |
| SECONDARY Phase 1 and 2: Change From Baseline in Bone Turn-over Marker - C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) |
0.034; 0.024; -0.270; 0.047; -0.036; 0.028 | — |
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).
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT03250676). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.