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OpenTrials
Terminated

NCT Number: NCT05827614

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

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.

Why the study stopped: Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.
Terminated

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Key information

Conditions

Triple Negative Breast Cancer (TNBC) Anogenital Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Squamous Cell Cervical Squamous Cell Carcinoma Cutaneous Squamous Cell Carcinoma (CSCC) ER+ Breast Cancer Head and Neck (HNSCC) Head and Neck Neoplasms High Grade Endometrial Carcinoma High Grade Serous Ovarian Carcinoma Histiocytoma Histiocytoma, Malignant Fibrous Leiomyosarcoma Leiomyosarcoma (LMS) Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Glandular and Epithelial Neoplasms, Muscle Tissue Pancreatic Cancer Metastatic Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Small Cell Lung Cancer Small Cell Lung Carcinoma Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Triple Negative Breast Neoplasms Undifferentiated Pleomorphic Sarcoma (UPS)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

UCLA Medical Center, Los Angeles, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 exclusion criteria per study protocol.

Treatment and study plan

BBI-355

Drug

Oral CHK1 inhibitor

Erlotinib

Drug

EGFR Inhibitor

Futibatinib

Drug

FGFR1-4 Inhibitor

BBI-825

Drug

Oral RNR Inhibitor

Primary outcomes

  1. 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

    Time frame: 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.

  2. 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

    Time frame: 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 outcomes

  1. Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825

    Time frame: 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.

  2. Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib, and BBI-825

    Time frame: 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.

  3. Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825

    Time frame: 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.

  4. Area under the concentration time curve (AUC) of BBI-355, erlotinib, futibatinib, and BBI-825

    Time frame: 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.

  5. Anti-tumor activity of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Boundless Bio, Inc.

Industry

Registry information

Official study title

An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications

Acronym: POTENTIATE

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Apr 25, 2023
Registry last updated
Aug 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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