University of Kansas Medical Center

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

Purpose

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.

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

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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.

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

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Single Agent Dose Escalation	Single agent BBI-355, administered orally in 28-day cycles	Drug: BBI-355 Oral CHK1 inhibitor
Experimental Single Agent Dose Expansion	Single agent BBI-355, administered orally in 28-day cycles	Drug: BBI-355 Oral CHK1 inhibitor
Experimental Dose Escalation in Combination with EGFR Inhibitor	Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.	Drug: BBI-355 Oral CHK1 inhibitor Drug: Erlotinib EGFR Inhibitor
Experimental Dose Escalation in Combination with FGFR Inhibitor	Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.	Drug: BBI-355 Oral CHK1 inhibitor Drug: Futibatinib FGFR1-4 Inhibitor
Experimental Dose Escalation in Combination with RNR Inhibitor	Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.	Drug: BBI-355 Oral CHK1 inhibitor Drug: BBI-825 Oral RNR Inhibitor

More Details

Status: Active, not recruiting
Sponsor: Boundless Bio

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.