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 (POTENTIATE)

January 21, 2026 updated by: Boundless Bio

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

85

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology
    • Colorado
      • Denver, Colorado, United States, 80218
        • HealthONE
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Florida Cancer Specialists
    • Kansas
      • Fairway, Kansas, United States, 66205
        • The University of Kansas
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Start Midwest
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI Oncology Partners
    • Texas
      • Houston, Texas, United States, 77054
        • MD Anderson Cancer Center
      • Irving, Texas, United States, 75039
        • Next Oncology - Dallas
      • San Antonio, Texas, United States, 78229
        • NEXT Oncology
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • NEXT Oncology
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington, Fred Hutchinson Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
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.
Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
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.
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
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.
Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)
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.
1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boundless Bio

Investigators

  • Study Director: Robert Doebele, MD, PhD, Boundless Bio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

March 27, 2023

First Submitted That Met QC Criteria

April 12, 2023

First Posted (Actual)

April 25, 2023

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBI-355-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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