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

Solid Tumor Clinical Trial

— STARMAP  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06299761
• Other study ID #: BBI-825-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 28, 2024
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: Boundless Bio
• Contact: Sara Weymer
• Phone: 16198211090
• Email: ClinicalDevelopment[@]boundlessbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• BBI-825
Oral RNR inhibitor

Locations

Country	Name	City	State
United States	START Midwest	Grand Rapids	Michigan
United States	NEXT Oncology	San Antonio	Texas
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Boundless Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)