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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor
• Interventions: Drug: BBI-825

• Registration Number: NCT06299761
• Lead Sponsor: Boundless Bio

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.

Study Timeline

• Study First Submitted: 2024-02-26
• Study First Submitted QC: 2024-03-07
• Study First Posted: 2024-03-08
• Study Start: 2024-03-28
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-11
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 42

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 exclusion criteria per study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single Agent Dose Escalation	BBI-825	Single agent BBI-825, administered orally, twice daily, in 28-day cycles

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.

Trial Locations

Locations (4)

Sarcoma Oncology Research Center; 🇺🇸 Santa Monica, California, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States