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

ArmDescriptionAssigned 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.