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). BBI-825 is an oral, potent, selective ribonucleotide reductase (or RNR) small molecule inhibitor. This is a first-in-human, open-label, 2-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 BBI-825 or other select therapies.
BBI-355 and BBI-825 are 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
Oral CHK1 inhibitor
EGFR Inhibitor
FGFR1-4 Inhibitor
Oral RNR Inhibitor
UCLA Medical Center
Los Angeles, California, United States
Sarcoma Oncology
Santa Monica, California, United States
HealthONE
Denver, Colorado, United States
Florida Cancer Specialists
Lake Mary, Florida, United States
The University of Kansas
Fairway, Kansas, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
START Midwest
Grand Rapids, Michigan, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
...and 6 more locations
Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 as a single agent and in combination with each of the following agents: erlotinib, futibatinib, or BBI-825
TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Time frame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825
The MTD and/or RP2D of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825 will be determined.
Time frame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825
Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825 will be determined.
Time frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib, and BBI-825
Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib and BBI-825 will be determined.
Time frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825
Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825 will be determined.
Time frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Area under the concentration time curve (AUC) of BBI-355, erlotinib, futibatinib, and BBI-825
Area under the concentration time curve (AUC) of BBI-355, erlotinib, futibatinib and BBI-825 will be determined.
Time frame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Anti-tumor activity of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825
Tumor response will be determined by RECISTv1.1.
Time frame: 1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days)
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