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Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

RecruitingPhase 1

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)

Who can join

Ages 18 and older · All sexes

Full 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

About the study

First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.

What is being tested

Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) · Participants: 392 · Started: Oct 29, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06625775

Locations in the U.S.

CaliforniaCity of Hope Comprehensive Cancer Center, Duarte
University of California Los Angeles, Los Angeles
University of California San Diego Moores Cancer Center, San Diego
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco
FloridaMoffitt Cancer Center, Tampa
IndianaIndiana University Simon Comprehensive Cancer Center, Indianapolis
MassachusettsDana-Farber Cancer Insitute, Boston
Massachusetts General Hospital, Boston
MissouriSt. Lukes Hospital of Kansas City, Kansas City
Washington University School of Medicine, St Louis
New YorkColumbia University Irving Medical Center, New York
Memorial Sloan Kettering Cancer Center, New York
TennesseeSCRI Oncology Partners, Nashville
TexasSCRI at Mary Crowley, Dallas
University of Texas Southwestern Medical Center, Dallas
The University of Texas MD Anderson Cancer Center, Houston
University of Texas San Antonio (UTSA), San Antonio
WashingtonFred Hutchinson Cancer Center, Seattle
WisconsinWisconsin Institute for Medical Research, Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.