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Study of the Kinesin Oral Molecular Degrader BBI-940 in Subjects With Advanced or Metastatic Breast Cancer

NCT07408089 · Boundless Bio, Inc.
In plain English

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Official title
An Open-Label, Multicenter, First-in-Human, Phase 1 Study of BBI-940 in Advanced or Metastatic Breast Cancer: Kinesin Oral Molecular Degrader for Oncology (KOMODO-1)
About this study
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.
Eligibility criteria
Key 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. Key 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
Enrollment target: 96 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2026-02-25
Estimated completion: 2029-05-31
Last updated: 2026-04-13
Interventions
Drug: BBI-940Drug: Fulvestrant
Primary outcomes
  • Rate of dose limiting toxicities (DLTs) in each BBI-940 monotherapy dose escalation cohort. (First 28 days of study treatment (through end of Cycle 1).)
  • Incidence of treatment emergent adverse events (TEAEs) in each dose group and overall as assessed by CTCAE version 5.0. (First dose of study treatment through 30 days after the last dose of study treatment.)
  • Incidence of study treatment discontinuation and/or interruption by dose group and overall. (First dose of study treatment through 30 days after the last dose of study treatment.)
Sponsor
Boundless Bio, Inc. · industry
Contacts & investigators
ContactAngela Pietrofeso · contact · clinicaltrials@boundlessbio.com · 1-619-821-1090
ContactRebecca Reynolds · contact · clinicaltrials@boundlessbio.com · 1-619-821-1090
InvestigatorRobert C. Doebele, MD, PhD · study_director, Boundless Bio, Inc.
All locations (8)
The START Center for Cancer ResearchRecruiting
Los Angeles, California, United States
The START Center for Cancer ResearchRecruiting
Lake Success, New York, United States
NEXT OncologyRecruiting
Austin, Texas, United States
University of Texas Southwestern Medical CenterRecruiting
Dallas, Texas, United States
NEXT OncologyRecruiting
Houston, Texas, United States
NEXT OncologyRecruiting
San Antonio, Texas, United States
The START Center for Cancer CareRecruiting
San Antonio, Texas, United States
NEXT OncologyRecruiting
Fairfax, Virginia, United States
Study of the Kinesin Oral Molecular Degrader BBI-940 in Subjects With Advanced or Metastatic Breast Cancer · TrialPath