Clinical trial · Interventional
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
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
NCT05827614CI-TRIAL-00122823POTENTIATEterminatedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.
Summary
Brief summary (as posted)
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
Conditions (12)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Anogenital Cancer | — | UNRESOLVED | — |
| Cervical Squamous Cell Carcinoma | Cervical Squamous Cell Carcinoma | CURATED_BROADER | 0.80 |
| Cutaneous Squamous Cell Carcinoma (CSCC) | Skin Squamous Cell Carcinoma | ALIAS | 0.85 |
| ER+ Breast Cancer | — | UNRESOLVED | — |
| Head and Neck (HNSCC) | Head and Neck Squamous Cell Carcinoma | ALIAS | 0.85 |
| High Grade Endometrial Carcinoma | High Grade Endometrial Carcinoma | ONTOLOGY_EXACT | 0.98 |
| High Grade Serous Ovarian Carcinoma | — | UNRESOLVED | — |
| Leiomyosarcoma (LMS) | Leiomyosarcoma |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| BBI-355 | Drug | — | UNRESOLVED |
| BBI-825 | Drug | — | UNRESOLVED |
| Erlotinib | Drug | Erlotinib | ALIAS |
| Futibatinib | Drug | Futibatinib | ALIAS |
Design
Arms and outcomes
Arms (5)
- type
- EXPERIMENTAL
- label
- Single Agent Dose Escalation
- description
- Single agent BBI-355, administered orally in 28-day cycles
- interventionNames
- Drug: BBI-355
- type
- EXPERIMENTAL
- label
- Single Agent Dose Expansion
- description
- Single agent BBI-355, administered orally in 28-day cycles
- interventionNames
- Drug: BBI-355
- type
- EXPERIMENTAL
- label
- Dose Escalation in Combination with EGFR Inhibitor
- description
- Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (7)
- BACKGROUNDJones 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. PMID 36378548
- BACKGROUNDItaliano 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. PMID 29788155
- BACKGROUNDTang 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. PMID 39506153
- BACKGROUNDWu 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. PMID 34752712
- BACKGROUNDTurner 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. PMID 28178237