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

Summary

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.

Eligibility

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.

Conditions4

Locations5 sites

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