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

• ClinicalTrials.gov Identifier: NCT06299761
• Recruitment Status: Recruiting
• First Posted: March 8, 2024
• Last Update Posted: April 29, 2024
• Sponsor: Boundless Bio
• Information provided by (Responsible Party): Boundless Bio

Tracking Information

• First Submitted Date: February 26, 2024
• First Posted Date: March 8, 2024
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: March 28, 2024
• Estimated Primary Completion Date: February 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2024)

• Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-825 [ Time Frame: 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 [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 7, 2024)

• Maximum observed plasma concentration (Cmax) of BBI-825 [ Time Frame: 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 [ 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-825 will be determined.
• Time to Cmax (Tmax) of BBI-825 [ Time Frame: 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 [ 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-825 will be determined.
• Anti-tumor activity of BBI-825 as determined by RECISTv1.1 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the RNR Inhibitor BBI-825 in Subjects With Tumors With Resistance Gene Amplifications
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

BBI-825 single agent dose escalation

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Solid Tumor

Intervention

Drug: BBI-825

Oral RNR inhibitor

Other Name: ribonucleotide reductase inhibitor

Study Arms

Experimental: Single Agent Dose Escalation

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

Intervention: Drug: BBI-825

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 7, 2024): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2027
• Estimated Primary Completion Date: February 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sara Weymer; 16198211090; ClinicalDevelopment@boundlessbio.com

Contact: Swadesh Sharma; 16198211090; ClinicalDevelopment@boundlessbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06299761
• Other Study ID Numbers: BBI-825-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Boundless Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Boundless Bio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Klaus Wagner, MD; Boundless Bio

• PRS Account: Boundless Bio
• Verification Date: April 2024