Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), and the RNR Inhibitor BBI-825, in Subjects With Tumors With Oncogene Amplifications

NCT ID: NCT05827614

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-24
• Study Completion Date: 2027-03-31

Brief Summary

BBI-355 is an oral, potent, selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). BBI-825 is an oral, potent, selective ribonucleotide reductase (or RNR) small molecule inhibitor. This is a first-in-human, open-label, 2-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with BBI-825 or other select therapies.

Detailed Description

BBI-355 and BBI-825 are administered orally in various dosing schedules to subjects with locally advanced or metastatic non-resectable solid tumors harboring oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

Conditions

Triple Negative Breast Cancer (TNBC); High Grade Serous Ovarian Carcinoma; High Grade Endometrial Carcinoma; Anogenital Cancer; Head and Neck (HNSCC); Cutaneous Squamous Cell Carcinoma (CSCC); Cervical Squamous Cell Carcinoma; ER+ Breast Cancer; Leiomyosarcoma (LMS); Undifferentiated Pleomorphic Sarcoma (UPS); Pancreatic Cancer Metastatic; Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Agent Dose Escalation

Single agent BBI-355, administered orally in 28-day cycles

Group Type: EXPERIMENTAL

BBI-355

Intervention Type: DRUG

Oral CHK1 inhibitor

Single Agent Dose Expansion

Single agent BBI-355, administered orally in 28-day cycles

Group Type: EXPERIMENTAL

BBI-355

Intervention Type: DRUG

Oral CHK1 inhibitor

Dose Escalation in Combination with EGFR Inhibitor

Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.

Group Type: EXPERIMENTAL

BBI-355

Intervention Type: DRUG

Oral CHK1 inhibitor

Erlotinib

Intervention Type: DRUG

EGFR Inhibitor

Dose Escalation in Combination with FGFR Inhibitor

Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.

Group Type: EXPERIMENTAL

BBI-355

Intervention Type: DRUG

Oral CHK1 inhibitor

Futibatinib

Intervention Type: DRUG

FGFR1-4 Inhibitor

Dose Escalation in Combination with RNR Inhibitor

Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.

Group Type: EXPERIMENTAL

BBI-355

Intervention Type: DRUG

Oral CHK1 inhibitor

BBI-825

Intervention Type: DRUG

Oral RNR Inhibitor

Interventions

BBI-355

Oral CHK1 inhibitor

Intervention Type: DRUG

Erlotinib

EGFR Inhibitor

Intervention Type: DRUG

Futibatinib

FGFR1-4 Inhibitor

Intervention Type: DRUG

BBI-825

Oral RNR Inhibitor

Intervention Type: DRUG

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,
• Evidence of oncogene amplification,
• 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,

Exclusion Criteria

• Single agent arm: Prior exposure to CHK1 or WEE1 inhibitors,
• BBI-355 combination with BBI-825 arm: Prior exposure to combination therapy of any RNR inhibitor plus CHK1/2 inhibitor,
• 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,
• Prior organ allograft transplantations or allogeneic peripheral blood stem cell/bone marrow transplantation,

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boundless Bio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Doebele, MD, PhD

Role: STUDY_DIRECTOR

Boundless Bio

Locations

UCLA Medical Center

Los Angeles, California, United States

Sarcoma Oncology

Santa Monica, California, United States

HealthONE

Denver, Colorado, United States

Florida Cancer Specialists

Lake Mary, Florida, United States

The University of Kansas

Fairway, Kansas, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

START Midwest

Grand Rapids, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology - Dallas

Irving, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

NEXT Oncology

Fairfax, Virginia, United States

University of Washington, Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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Other Identifiers

BBI-355-101

Identifier Type: -

Identifier Source: org_study_id