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

Phase 1

Recruiting

• 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)
• Interventions: Drug: BBI-355; Drug: Erlotinib; Drug: Futibatinib; Drug: BBI-825

• Registration Number: NCT05827614
• Lead Sponsor: Boundless Bio

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.

Study Timeline

• Study Start: 2023-03-24
• Study First Submitted: 2023-03-27
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-25
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-15
• Last Update Posted: 2025-07-18
• Primary Completion: 2026-09-30
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 127

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,
• Other inclusion criteria per study protocol.

Key

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,
• Other exclusion criteria per study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single Agent Dose Escalation	BBI-355	Single agent BBI-355, administered orally in 28-day cycles
Single Agent Dose Expansion	BBI-355	Single agent BBI-355, administered orally in 28-day cycles
Dose Escalation in Combination with EGFR Inhibitor	BBI-355	Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
Dose Escalation in Combination with EGFR Inhibitor	Erlotinib	Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
Dose Escalation in Combination with FGFR Inhibitor	BBI-355	Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
Dose Escalation in Combination with FGFR Inhibitor	Futibatinib	Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
Dose Escalation in Combination with RNR Inhibitor	BBI-355	Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.
Dose Escalation in Combination with RNR Inhibitor	BBI-825	Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.

Primary Outcome Measures

Name	Time	Method
Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 as a single agent and in combination with each of the following agents: erlotinib, futibatinib, or BBI-825	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-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825	Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)	The MTD and/or RP2D of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825 will be determined.

Secondary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)	Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825 will be determined.
Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib, and BBI-825	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)	Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib and BBI-825 will be determined.
Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825	Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)	Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825 will be determined.
Area under the concentration time curve (AUC) of BBI-355, erlotinib, futibatinib, and BBI-825	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-355, erlotinib, futibatinib and BBI-825 will be determined.
Anti-tumor activity of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825	1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days)	Tumor response will be determined by RECISTv1.1.

Trial Locations

Locations (16)

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

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

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