Overview
BBI-355 is an oral, potent, selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). This is a first-in-human, open-label, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with select therapies.
Description
BBI-355 is administered orally in various dosing schedules to subjects with locally advanced or metastatic non-resectable solid tumors harboring oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.
Eligibility
Key Inclusion Criteria:
- Locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists,
- Single agent arm: Evidence of oncogene amplification,
- BBI-355 combination with erlotinib arm: Evidence of amplification of wildtype EGFR,
- BBI-355 combination with futibatinib arm: Evidence of amplification of wildtype FGFR1, FGFR2, FGFR3, or FGFR4,
- Availability of FFPE tumor tissue, archival or newly obtained,
- Measurable disease as defined by RECIST Version 1.1,
- Adequate hematologic function,
- Adequate hepatic and renal function,
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1,
- Other inclusion criteria per study protocol.
Key Exclusion Criteria:
- Well-known tumor activating oncogene mutations or fusions,
- Prior exposure to CHK1 inhibitors,
- BBI-355 combination with erlotinib arm: Prior exposure to EGFR inhibitors,
- BBI-355 combination with futibatinib arm: Prior exposure to FGFR inhibitors,
- Hematologic malignancies,
- Primary CNS malignancy, leptomeningeal disease, or symptomatic active CNS metastases, with exceptions per study protocol,
- Prior or concurrent malignancies, with exceptions per study protocol,
- History of HBV, HCV, or HIV infection,
- Clinically significant cardiac condition,
- Active or history of interstitial lung disease (ILD) or pneumonitis, or history of ILD or pneumonitis requiring steroids or other immunosuppressive medications,
- QTcF > 470 msec,
- Prior organ allograft transplantations or allogeneic peripheral blood stem cell/bone marrow transplantation,
- Other exclusion criteria per study protocol.