Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), in Subjects With Tumors With Oncogene Amplifications
Purpose
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.
Conditions
- Non-small Cell Lung Cancer
- Non-Small Cell Lung Adenocarcinoma
- Non-Small Cell Squamous Lung Cancer
- Head and Neck Squamous Cell Carcinoma
- Esophageal Cancer
- Gastric Cancer
- Breast Cancer
- Bladder Cancer
- Ovarian Cancer
- Endometrial Cancer
- Liposarcoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Single Agent Dose Escalation |
Single agent BBI-355, administered orally in 28-day cycles |
|
|
Experimental Single Agent Dose Expansion |
Single agent BBI-355, administered orally in 28-day cycles |
|
|
Experimental Dose Escalation in Combination with EGFR Inhibitor |
Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles. |
|
|
Experimental Dose Escalation in Combination with FGFR Inhibitor |
Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles. |
|
Recruiting Locations
The University of Kansas
Fairway, Kansas 66205
Fairway, Kansas 66205
More Details
- Status
- Recruiting
- Sponsor
- Boundless Bio
Detailed 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.