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

NCT06299761 | Terminated Phase 1 FDA Drug

• 1 other identifier: BBI-825-101
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

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.

Conditions

Solid Tumor

Keywords

Amplification; Oncogene Amplification; ribonucleotide reductase inhibitor; RNR inhibitor

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of treatment emergent adverse events (TEAEs) of 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.

  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-825

  The MTD and/or RP2D of BBI-825 will be determined.

  Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)

Secondary Outcomes (5)

• Maximum observed plasma concentration (Cmax) 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

  Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

• Time to Cmax (Tmax) 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

  Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

• 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)

Study Arms (1)

Single Agent Dose Escalation

EXPERIMENTAL

Single agent BBI-825, administered orally, twice daily, in 28-day cycles

Drug: BBI-825

Interventions

BBI-825 DRUG

Oral RNR inhibitor

Also known as: ribonucleotide reductase inhibitor

Single Agent Dose Escalation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• Boundless Bio, Inc.: lead

Study Sites (5)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

NEXT Oncology

Irving, Texas, 75039, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Study Officials

• Robert Doebele, MD

  Boundless Bio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: BBI-825 single agent dose escalation

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 8, 2024
• Study Start: March 28, 2024
• Primary Completion: June 25, 2025
• Study Completion: June 25, 2025
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)