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Triple Negative Breast Cancer (TNBC)Phase 1POTENTIATENCT05827614

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

A Phase 1 study testing BBI-355, Erlotinib and Futibatinib in people with Triple Negative Breast Cancer (TNBC) and High Grade Serous Ovarian Carcinoma, run by Boundless Bio, Inc. at 16 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BBI-355, Erlotinib and Futibatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
16 sitesUnited States
Study dates
24 Mar 2023to 17 Mar 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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,
Show all 11Show fewer
  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • HealthONE

    Denver, Colorado, 80218

  • NEXT Oncology

    Fairfax, Virginia, 22031

  • The University of Kansas

    Fairway, Kansas, 66205

  • START Midwest

    Grand Rapids, Michigan, 49546

  • MD Anderson Cancer Center

    Houston, Texas, 77054

  • NEXT Oncology - Dallas

    Irving, Texas, 75039

  • Florida Cancer Specialists

    Lake Mary, Florida, 32746

  • UCLA Medical Center

    Los Angeles, California, 90095

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • NEXT Oncology

    San Antonio, Texas, 78229

  • Sarcoma Oncology

    Santa Monica, California, 90403

  • University of Washington, Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official 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

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.

Read the 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.

Being tested
BBI-355, Erlotinib, Futibatinib, BBI-825
Keywords
ecDNA, extrachromosomal DNA, Amplification, Oncogene Amplification, Checkpoint kinase 1, CHK1, RNR, ribonucleotide reductase
Medical subject headings
Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck, Leiomyosarcoma, Histiocytoma, Malignant Fibrous, Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BBI-355Drug

    Oral CHK1 inhibitor

  • ErlotinibDrug

    EGFR Inhibitor

  • FutibatinibDrug

    FGFR1-4 Inhibitor

  • BBI-825Drug

    Oral RNR Inhibitor

Study groups in NCT05827614
Study groupRoleWhat they receive
Single Agent Dose EscalationExperimentalSingle agent BBI-355, administered orally in 28-day cycles
Receives: Drug: BBI-355
Single Agent Dose ExpansionExperimentalSingle agent BBI-355, administered orally in 28-day cycles
Receives: Drug: BBI-355
Dose Escalation in Combination with EGFR InhibitorExperimentalCombination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
Receives: Drug: BBI-355; Drug: Erlotinib
Dose Escalation in Combination with FGFR InhibitorExperimentalCombination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
Receives: Drug: BBI-355; Drug: Futibatinib
Dose Escalation in Combination with RNR InhibitorExperimentalCombination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.
Receives: Drug: BBI-355; Drug: BBI-825

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

    Measured: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)

  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

    The MTD and/or RP2D of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825 will be determined.

    Measured: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)

Secondary outcomes (5)

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

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

    Measured: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

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

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

    Measured: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

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

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

    Measured: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

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

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

    Measured: Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days)

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

    Tumor response will be determined by RECISTv1.1.

    Measured: 1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2023
  2. Study start24 Mar 2023
  3. Primary completion17 Mar 2026
  4. Study completion17 Mar 2026

Why it 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.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
BBI-355 single agent dose escalation and expansion, and BBI-355 dose escalation in combination with select targeted therapies.
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05827614
Sponsor's protocol ID
BBI-355-101
Acronym
POTENTIATE
Status last verified
Jun 2026
First submitted
27 Mar 2023
Last updated
19 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jones R, Plummer R, Moreno V, Carter L, Roda D, Garralda E, Kristeleit R, Sarker D, Arkenau T, Roxburgh P, Walter HS, Blagden S, Anthoney A, Klencke BJ, Kowalski MM, Banerji U. A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer. Clin Cancer Res. 2023 Jan 17;29(2):331-340. doi: 10.1158/1078-0432.CCR-22-2074.

    PubMed 36378548

  • Italiano A, Infante JR, Shapiro GI, Moore KN, LoRusso PM, Hamilton E, Cousin S, Toulmonde M, Postel-Vinay S, Tolaney S, Blackwood EM, Mahrus S, Peale FV, Lu X, Moein A, Epler J, DuPree K, Tagen M, Murray ER, Schutzman JL, Lauchle JO, Hollebecque A, Soria JC. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. Ann Oncol. 2018 May 1;29(5):1304-1311. doi: 10.1093/annonc/mdy076.

    PubMed 29788155

  • Tang J, Weiser NE, Wang G, Chowdhry S, Curtis EJ, Zhao Y, Wong IT, Marinov GK, Li R, Hanoian P, Tse E, Mojica SG, Hansen R, Plum J, Steffy A, Milutinovic S, Meyer ST, Luebeck J, Wang Y, Zhang S, Altemose N, Curtis C, Greenleaf WJ, Bafna V, Benkovic SJ, Pinkerton AB, Kasibhatla S, Hassig CA, Mischel PS, Chang HY. Enhancing transcription-replication conflict targets ecDNA-positive cancers. Nature. 2024 Nov;635(8037):210-218. doi: 10.1038/s41586-024-07802-5. Epub 2024 Nov 6.

    PubMed 39506153

  • Wu S, Bafna V, Chang HY, Mischel PS. Extrachromosomal DNA: An Emerging Hallmark in Human Cancer. Annu Rev Pathol. 2022 Jan 24;17:367-386. doi: 10.1146/annurev-pathmechdis-051821-114223. Epub 2021 Nov 9.

    PubMed 34752712

  • Turner KM, Deshpande V, Beyter D, Koga T, Rusert J, Lee C, Li B, Arden K, Ren B, Nathanson DA, Kornblum HI, Taylor MD, Kaushal S, Cavenee WK, Wechsler-Reya R, Furnari FB, Vandenberg SR, Rao PN, Wahl GM, Bafna V, Mischel PS. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 2017 Mar 2;543(7643):122-125. doi: 10.1038/nature21356. Epub 2017 Feb 8.

    PubMed 28178237

  • Lange JT, Rose JC, Chen CY, Pichugin Y, Xie L, Tang J, Hung KL, Yost KE, Shi Q, Erb ML, Rajkumar U, Wu S, Taschner-Mandl S, Bernkopf M, Swanton C, Liu Z, Huang W, Chang HY, Bafna V, Henssen AG, Werner B, Mischel PS. The evolutionary dynamics of extrachromosomal DNA in human cancers. Nat Genet. 2022 Oct;54(10):1527-1533. doi: 10.1038/s41588-022-01177-x. Epub 2022 Sep 19.

    PubMed 36123406

  • Kim H, Nguyen NP, Turner K, Wu S, Gujar AD, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin SB, Yi E, Menghi F, Schulte JH, Henssen AG, Chang HY, Beck CR, Mischel PS, Bafna V, Verhaak RGW. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat Genet. 2020 Sep;52(9):891-897. doi: 10.1038/s41588-020-0678-2. Epub 2020 Aug 17.

    PubMed 32807987

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BBI-355, Erlotinib and Futibatinib in people with Triple Negative Breast Cancer (TNBC) and High Grade Serous Ovarian Carcinoma, run by Boundless Bio, Inc. at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05827614, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.

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