Recruiting

Phase 1

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

Sponsor:

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Code:

NCT06625775

Conditions

Solid Tumor, Adult

Metastatic Breast Cancer

Advanced Breast Cancer

HER2 Mutation-Related Tumors

HER2-positive Metastatic Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BBO-10203

Trastuzumab

Fulvestrant

Ribociclib

FOLFOX

Study Details

Brief summary:

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.

Conditions

Solid Tumor, Adult

Metastatic Breast Cancer

Advanced Breast Cancer

HER2 Mutation-Related Tumors

HER2-positive Metastatic Breast Cancer

Study ID

NCT06625775

Start date

Oct 29, 2024

Status verified date

Jun, 2026

Completion date

Nov, 2028

Anticipated

Primary completion date

Nov, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

392 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: BBO-10203

Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily as monotherapy. This cohort will enroll patients with HER2-positive advanced breast cancer, HR-positive HER2-negative advanced breast cancer, advanced colorectal cancer, and advanced lung cancer.

experimental: BBO-10203 + Trastuzumab

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab. This cohort will enroll patients with HER2-positive advanced breast cancer.

experimental: BBO-10203 + Fulvestrant

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

experimental: BBO10203 + Fulvestrant + Ribociclib

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant and ribociclib as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

experimental: BBO10203 + FOLFOX + Bevacizumab

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.

Interventions

BBO-10203

Participants will receive assigned dose of BBO-10203 orally once daily

Trastuzumab

Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days

Fulvestrant

Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)

Ribociclib

Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)

FOLFOX

Patients will receive FOLFOX as infusion every 14 days

Bevacizumab

Patients will receive bevacizumab as infusion every 28 days

Primary outcome measure

Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent [ Time Frame: Up to approximately 5 years ]
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) [ Time Frame: Up to approximately 5 years ]
Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab [ Time Frame: Up to approximately 5 years ]

Central Contacts and Locations

Central contacts

BBOT (BridgeBio Oncology Therapeutics)

650-405-8440 Breaker-101ct.gov@bridgebiooncology.com

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90095

University of California San Diego Moores Cancer Center

Recruiting

San Diego, California, United States, 92093

UCSF Helen Diller Family Comprehensive Cancer Center

Recruiting

San Francisco, California, United States, 94158

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Indiana University Simon Comprehensive Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Insitute

Recruiting

Boston, Massachusetts, United States, 02215

St. Lukes Hospital of Kansas City

Recruiting

Kansas City, Missouri, United States, 64111

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

SCRI at Mary Crowley

Recruiting

Dallas, Texas, United States, 75230

University of Texas Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

University of Texas San Antonio (UTSA)

Recruiting

San Antonio, Texas, United States, 78229

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Wisconsin Institute for Medical Research

Recruiting

Madison, Wisconsin, United States, 53792

More Information

Sponsor

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Last update posted

Jun 23, 2026

Last verified

Jun, 2026

Keywords

BREAKER-101
BridgeBio Oncology Therapeutics
BBOT
Phase1
Phase 1a/1b
Trastuzumab
Breast
Colorectal
Non-Small Cell Lung Cancer
CRC
NSCLC
Metastatic Cancer
Advanced Cancer
HER2-positive
HR-positive
HR-positive, HER2-negative
HER2-negative

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) on 2026-06-23.