Solid Tumor
Conditions
Keywords
Amplification, Oncogene Amplification, ribonucleotide reductase inhibitor, RNR inhibitor
Brief summary
BBI-825 is a potent, selective, oral, small molecule inhibitor of ribonucleotide reductase (RNR). This is a first-in-human, open-label, non-randomized, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-825 administered as a single agent and in combination with select targeted therapies.
Detailed description
BBI-825 will be administered orally (PO) twice daily (BID) to subjects with 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.
Interventions
DRUGBBI-825
Oral RNR inhibitor
Sponsors
Boundless Bio, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
BBI-825 single agent dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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, * 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 chemotherapies with nonselective RNR inhibitory activity e.g., gemcitabine is permitted), * Receipt of any approved or considered standard of care anticancer drug(s) or biological product(s) within 4 weeks or 5 half-lives, * 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, * Concurrent use of strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, or CYP2C19, * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-825 | Start of Cycle 1 until 30 days following last dose (each cycle is 28 days) | TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. |
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-825 | Start of Cycle 1 until 30 days following last dose (each cycle is 28 days) | The MTD and/or RP2D of BBI-825 will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) of BBI-825 | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | Maximum observed plasma concentration (Cmax) of BBI-825 will be determined. |
| Trough observed plasma concentration (Ctrough) of BBI-825 | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | Trough observed plasma concentration (Ctrough) of BBI-825 will be determined. |
| Time to Cmax (Tmax) of BBI-825 | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | Time to Cmax (Tmax) of BBI-825 will be determined. |
| Area under the concentration time curve (AUC) of BBI-825 | 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-825 will be determined. |
| Anti-tumor activity of BBI-825 as determined by RECISTv1.1 | Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days) | Number of participants achieving a best response of progressive disease, stable disease, partial response, or complete response. |
Countries
United States
Contacts
STUDY_DIRECTORRobert Doebele, MD
Boundless Bio, Inc.
Outcome results
None listed