Anogenital Cancer, Cervical Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma (CSCC), ER+ Breast Cancer, Head and Neck (HNSCC), High Grade Endometrial Carcinoma, High Grade Serous Ovarian Carcinoma, Leiomyosarcoma (LMS), Pancreatic Cancer Metastatic, Small Cell Lung Cancer, Triple Negative Breast Cancer (TNBC), Undifferentiated Pleomorphic Sarcoma (UPS)
Conditions
Keywords
ecDNA, extrachromosomal DNA, Amplification, Oncogene Amplification, Checkpoint kinase 1, CHK1, RNR, ribonucleotide reductase
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.
Interventions
DRUGBBI-355
Oral CHK1 inhibitor
DRUGErlotinib
EGFR Inhibitor
DRUGFutibatinib
FGFR1-4 Inhibitor
DRUGBBI-825
Oral RNR Inhibitor
Sponsors
Boundless Bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
STUDY_DIRECTORRobert Doebele, MD, PhD
Boundless Bio, Inc.
Outcome results
None listed