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 2, 2024
• Sponsor: Boundless Bio
• Information provided by (Responsible Party): Boundless Bio

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: BBI-825	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: BBI-825 single agent dose escalation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 28, 2024
• Estimated Primary Completion Date: February 2027
• Estimated Study Completion Date: February 2027

Arms and Interventions

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 Name: ribonucleotide reductase inhibitor

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

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

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

Locations

United States, California

Sarcoma Oncology Research Center; Recruiting

Santa Monica, California, United States, 90403

United States, Texas

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Boundless Bio

Investigators

• Study Director: Klaus Wagner, MD; Boundless Bio

More Information

• Responsible Party: Boundless Bio
• ClinicalTrials.gov Identifier: NCT06299761
• Other Study ID Numbers: BBI-825-101
• First Posted: March 8, 2024
• Last Update Posted: April 2, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Boundless Bio:

Amplification; Oncogene Amplification; ribonucleotide reductase inhibitor; RNR inhibitor