Clinical trial NCT06299761: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Amplification
Oncogene Amplification
ribonucleotide reductase inhibitor
RNR inhibitor
Lead sponsor: Boundless Bio
Sponsor class: INDUSTRY
First posted: 2024-03-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: BBI-825 single agent dose escalation
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-825
timeFrame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-825
timeFrame: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of BBI-825
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Trough observed plasma concentration (Ctrough) of BBI-825
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Time to Cmax (Tmax) of BBI-825
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Area under the concentration time curve (AUC) of BBI-825
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
measure: Anti-tumor activity of BBI-825 as determined by RECISTv1.1
timeFrame: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Irving
country: United States
facility: NEXT Oncology
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Boundless Bio
name: Robert Doebele, MD
role: STUDY_DIRECTOR
References: