Study of the CHK1 Inhibitor BBI-355, an EcDNA-directed Therapy (ecDTx), in Subjects with Tumors with Oncogene Amplifications

About

Brief Summary

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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,