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

An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-825 and BBI-825 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Resistance Gene Amplifications

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: BBI-825

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Irving, Texas, United States, 75039
      • NEXT Oncology
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Agent Dose Escalation; Single agent BBI-825, administered orally, twice daily, in 28-day cycles	Drug: BBI-825; Oral RNR inhibitor; Other Names: ribonucleotide reductase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of BBI-825	Maximum observed plasma concentration (Cmax) of BBI-825 will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Trough observed plasma concentration (Ctrough) of BBI-825	Trough observed plasma concentration (Ctrough) of BBI-825 will be determined.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Time to Cmax (Tmax) of BBI-825	Time to Cmax (Tmax) of BBI-825 will be determined.	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	Area under the concentration time curve (AUC) of BBI-825 will be determined.	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	Number of participants achieving a best response of progressive disease, stable disease, partial response, or complete response.	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Boundless Bio
• Investigators: Study Director: Robert Doebele, MD, Boundless Bio

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Actual): June 25, 2025
• Study Completion (Actual): June 25, 2025

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Amplification; Oncogene Amplification; ribonucleotide reductase inhibitor; RNR inhibitor
• Other Study ID Numbers: BBI-825-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No