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Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors
NCT06625775 · TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
In plain English
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Official title
A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)
About this study
This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and PK of BBO-10203 as a single agent and in combination with Trastuzumab, Fulvestrant +/- Ribociclib, or FOLFOX + Bevacizumab in patients with locally advanced unresectable or metastatic (ie, advanced) solid tumors. The study includes a dose escalation phase and an expansion phase.
Eligibility criteria
Inclusion Criteria:
* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)
* Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
* Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)
* Stable brain metastases
* Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)
* Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy
* BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i
* BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted
* BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required
Exclusion Criteria:
* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors
* Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2)
* Patients with untreated and/or non-stable brain metastases
Other inclusion/exclusion criteria are specified in the protocol
Study design
Enrollment target: 392 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-10-29
Estimated completion: 2028-11
Last updated: 2026-04-13
Interventions
Drug: BBO-10203Drug: TrastuzumabDrug: FulvestrantDrug: RibociclibDrug: FOLFOXDrug: Bevacizumab
Primary outcomes
- • Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent (Up to approximately 5 years)
- • Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) (Up to approximately 5 years)
- • Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab (Up to approximately 5 years)
Sponsor
TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) · industry
Contacts & investigators
ContactBBOT (BridgeBio Oncology Therapeutics) · contact · Breaker-101ct.gov@bridgebiooncology.com · 650-405-8440
All locations (36)
City of Hope Comprehensive Cancer CenterRecruiting
Duarte, California, United States
University of California Los AngelesRecruiting
Los Angeles, California, United States
University of California San Diego Moores Cancer CenterRecruiting
San Diego, California, United States
UCSF Helen Diller Family Comprehensive Cancer CenterRecruiting
San Francisco, California, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Indiana University Simon Comprehensive Cancer CenterRecruiting
Indianapolis, Indiana, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InsituteRecruiting
Boston, Massachusetts, United States
St. Lukes Hospital of Kansas CityRecruiting
Kansas City, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Columbia University Irving Medical CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
SCRI at Mary CrowleyRecruiting
Dallas, Texas, United States
University of Texas Southwestern Medical CenterRecruiting
Dallas, Texas, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
University of Texas San Antonio (UTSA)Recruiting
San Antonio, Texas, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
Wisconsin Institute for Medical ResearchRecruiting
Madison, Wisconsin, United States
Scientia Clinical ResearchRecruiting
Randwick, New South Wales, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
Institut régional du Cancer de Montpellier - Val d'AurelleRecruiting
Montpellier, Occitanie, France
Institut Curie - René-Huguenin HospitalRecruiting
Saint-Cloud, Paris, France
lnstitut de Cancérologie de l'Ouest - Site Saint-HerblainRecruiting
Saint-Herblain, Pays de la Loire Region, France
Institut BergonieRecruiting
Bordeaux, France
Centre Léon BérardRecruiting
Lyon, France
Institut Gustave RoussyRecruiting
Villejuif, Île-de-France Region, France
Hospital Universitario Vall d'HebronRecruiting
Barcelona, Catalonia, Spain
Hospital Beata Maria AnaRecruiting
Madrid, Madrid, Spain
Hospital Quiron Madrid - NEXT OncologyRecruiting
Pozuelo de Alarcón, Madrid, Spain
IOB Institute of Oncology - Hospital Quironsalud BarcelonaRecruiting
Barcelona, Spain
START Barcelona - HM Nou Delfos HospitalRecruiting
Barcelona, Spain
Hospital Universitari Arnau de VilanovaRecruiting
Lleida, Spain
Hospital Universitario Fundación Jiménez DíazRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Universitari i Politècnic La FeRecruiting
Valencia, Spain