BBI-940 oral treatment for advanced or metastatic breast cancer

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)

This will try an oral drug called BBI-940, alone or with fulvestrant, in adults with advanced or metastatic ER+/HER2- breast cancer or certain triple-negative breast cancers.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Boundless Bio, Inc. (industry)
• Locations: 8 sites (Los Angeles, California and 7 other locations)
• Trial ID: NCT07408089 on ClinicalTrials.gov

What this trial studies

This first-in-human, open-label Phase 1 trial tests BBI-940, an oral kinesin molecular degrader, given as monotherapy or combined with fulvestrant in adults with advanced or metastatic breast cancer. Part 1 uses dose escalation to define safety, tolerability, and the recommended dose for expansion (RDE). Part 2 is dose expansion with predefined cohorts: Part 2A tests combination therapy in ER+/HER2- patients without ESR1 mutations, Part 2B tests monotherapy in ER+/HER2- patients with FGFR1 amplification, and Part 2C tests monotherapy in TNBC-LAR patients. Treatment is given in repeated 28-day cycles with protocol-specified safety monitoring and tumor/biomarker assessments.

Who should consider this trial

Good fit: Adults with locally advanced or metastatic ER+/HER2- breast cancer or TNBC-LAR who have received standard therapies, have measurable disease as required, and meet the study's molecular criteria (for example, no ESR1 mutation for the combination cohort or FGFR1 amplification for the monotherapy cohort) are the intended candidates.

Not a fit: Patients with early-stage disease, HER2-positive tumors, or those who do not meet the required molecular markers (such as lacking FGFR1 amplification or having an ESR1 mutation when excluded) are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, BBI-940 could provide a new oral targeted option that shrinks tumors or delays progression in certain advanced breast cancers.

How similar studies have performed: This is a first-in-human trial of a kinesin oral degrader, so the approach is novel, although targeted protein degraders have shown early promise in other cancer studies.

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.

Where this trial is running

Los Angeles, California and 7 other locations

• The START Center for Cancer Research — Los Angeles, California, United States (RECRUITING)
• The START Center for Cancer Research — Lake Success, New York, United States (RECRUITING)
• NEXT Oncology — Austin, Texas, United States (RECRUITING)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (RECRUITING)
• NEXT Oncology — Houston, Texas, United States (RECRUITING)
• NEXT Oncology — San Antonio, Texas, United States (RECRUITING)
• The START Center for Cancer Care — San Antonio, Texas, United States (RECRUITING)
• NEXT Oncology — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Angela Pietrofeso

Conditions: Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Phase 1, First in Human, BBI-940, Fulvestrant, FGFR1