Study of the Kinesin Oral Molecular Degrader BBI-940 in Subjects With Advanced or Metastatic Breast Cancer
Purpose
This is a first-in-human, open-label, Phase 1 study evaluating BBI-940, an investigational kinesin oral molecular degrader, administered as monotherapy or in combination with fulvestrant in adults with advanced or metastatic breast cancer.
Conditions
- Breast Cancer
- Metastatic Breast Cancer
- Advanced Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adults with locally advanced or metastatic breast cancer, including estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) disease or triple-negative breast cancer with luminal androgen receptor subtype (TNBC-LAR; androgen receptor expression ≥10% by immunohistochemistry), as applicable by study part. - Prior treatment with standard therapies known to provide clinical benefit, appropriate for disease subtype and study part, including endocrine therapy with CDK4/6 inhibition for ER+/HER2- disease. - Measurable disease per RECIST v1.1, except for participants enrolled in Part 1A. - Molecular eligibility as applicable by study part, including absence of an ESR1 mutation (Part 2A) or presence of FGFR1 amplification (Part 2B), based on prior local testing. - Availability of archival or newly obtained formalin-fixed, paraffin-embedded (FFPE) tumor tissue suitable for protocol-specified biomarker analyses. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Adequate hematologic, hepatic, renal, and coagulation function per protocol-defined laboratory criteria. - Estimated life expectancy of at least 12 weeks. - Ability to swallow oral medication and provide written informed consent.
Exclusion Criteria
- Prior exposure to an inhibitor or degrader of Kinesin. - Known hypersensitivity to study intervention(s) or excipients. - Receipt of recent anticancer therapy within protocol-defined washout periods. - Other active malignancy likely to interfere with study assessment. - Baseline QTcF >470 msec or congenital long QT syndrome. - Clinically significant pulmonary embolism within 6 weeks prior to first dose. - Major surgery within 4 weeks or minor surgery within 2 weeks prior to first dose. - Active infection requiring systemic therapy within 2 weeks prior to first dose. - Pregnant or breastfeeding, or planning conception or gamete donation during the study or required post-treatment period. - Prior solid organ transplant or allogeneic stem cell transplant with protocol-defined exceptions. - Failure to recover to CTCAE Grade ≤1 (or baseline) from prior anticancer therapy, with protocol-specified exceptions. - Any serious or uncontrolled medical, laboratory, or psychiatric condition that could compromise safety or study integrity. - Other exclusion criteria as specified in the study protocol.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- BBI-940 single agent dose escalation and expansion, and BBI-940 dose expansion (at multiple potential dose levels) in combination with fulvestrant.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Parts 1A, 1B. BBI-940 Monotherapy Escalation |
Participants receive BBI-940 given alone in multiple sequential dose escalation cohorts. BBI-940 is given orally in repeated 28-day cycles. |
|
|
Experimental Part 2A. BBI-940 in Combination with Fulvestrant (ER+/HER2- Breast Cancer without an ESR1 Mutation) |
Participants receive BBI-940 in combination with fulvestrant. BBI-940 is given orally in repeated 28-day cycles at one of multiple potential dose levels. |
|
|
Experimental Part 2B. BBI-940 Monotherapy Expansion (ER+/HER2- Breast Cancer with FGFR1 Amplification) |
Participants receive BBI-940 given alone at the recommended dose for expansion (RDE). BBI-940 is given orally in repeated 28-day cycles. |
|
|
Experimental Part 2C. BBI-940 Monotherapy Expansion (TNBC-LAR) |
Participants receive BBI-940 given alone at the recommended dose for expansion (RDE). BBI-940 is given orally in repeated 28-day cycles. |
|
Recruiting Locations
Austin 4671654, Texas 4736286 78758
Houston 4699066, Texas 4736286 77054
San Antonio 4726206, Texas 4736286 78229
San Antonio 4726206, Texas 4736286 78229
Fairfax 4758023, Virginia 6254928 22031
More Details
- Status
- Recruiting
- Sponsor
- Boundless Bio, Inc.
Detailed Description
The study consists of two parts: Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is a dose-escalation phase designed to evaluate the safety and tolerability of BBI-940 and to determine the recommended dose for expansion (RDE). Participants may have estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer or triple-negative breast cancer of the luminal androgen receptor subtype (TNBC-LAR). Part 2 is a dose-expansion phase designed to further evaluate BBI-940 at the selected RDE in defined participant populations. Part 2A evaluates BBI-940 in combination with fulvestrant, including multiple dose cohorts to evaluate the safety of the combination regimen and to determine the combination RDE in participants with ER+/HER2- breast cancer without an ESR1 mutation. Part 2B evaluates BBI-940 monotherapy at the RDE in participants with ER+/HER2- breast cancer with FGFR1 amplification. Part 2C evaluates BBI-940 monotherapy at the RDE in participants with TNBC-LAR. Across all parts of the study, treatment is administered in repeated 28-day cycles, and participants undergo protocol-specified safety assessments.