Study of the RNR Inhibitor BBI-825 in Subjects with Tumors with Resistance Gene Amplifications

Inclusion Criteria:

• Locally advanced or metastatic non-resectable solid tumors, whose disease hasprogressed despite all standard therapies or for whom no further standard orclinically acceptable therapy exists,

• 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:

• Prior exposure to a selective RNR inhibitor (Note: Prior exposure to chemotherapieswith nonselective RNR inhibitory activity e.g., gemcitabine is permitted),

• Receipt of any approved or considered standard of care anticancer drug(s) orbiological product(s) within 4 weeks or 5 half-lives,

• Hematologic malignancies,

• Primary CNS malignancy, leptomeningeal disease, or symptomatic active CNSmetastases, 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 ofILD or pneumonitis requiring steroids or other immunosuppressive medications,

• QTcF > 470 msec,

• Concurrent use of strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, orCYP2C19,

• Other exclusion criteria per study protocol.