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

September 2, 2026 updated by: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

392

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Scientia Clinical Research
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
  • Brazil
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062
        • Recruiting
        • Liga Contra o Câncer
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90470
        • Recruiting
        • Futtura Oncologia
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610
        • Recruiting
        • Hospital Sao Lucas da PUCRS
    • São Paulo
      • Sorocaba, São Paulo, Brazil, 18056
        • Recruiting
        • IEPE - Unimed Sorocaba
      • São Paulo, São Paulo, Brazil, 01317
        • Recruiting
        • Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
      • São Paulo, São Paulo, Brazil, 01246
        • Recruiting
        • Instituto do Câncer do Estado de São Paulo - ICESP
  • France
      • Bordeaux, France, 33000
        • Recruiting
        • Institut Bergonie
      • Lyon, France, 69008
        • Recruiting
        • Centre Léon Bérard
    • Occitanie
      • Montpellier, Occitanie, France, 34298
        • Recruiting
        • Institut régional du Cancer de Montpellier - Val d'Aurelle
    • Paris
      • Saint-Cloud, Paris, France, 92210
        • Recruiting
        • Institut Curie - René-Huguenin Hospital
    • Pays de la Loire Region
      • Saint-Herblain, Pays de la Loire Region, France, 44805
        • Recruiting
        • lnstitut de Cancérologie de l'Ouest - Site Saint-Herblain
    • Île-de-France Region
      • Villejuif, Île-de-France Region, France, 94805
        • Recruiting
        • Institut Gustave Roussy
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
    • Seoul
      • Seoul, Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center (AMC)
  • Spain
      • Barcelona, Spain, 08023
        • Recruiting
        • IOB Institute of Oncology - Hospital Quironsalud Barcelona
      • Barcelona, Spain, 08023
        • Recruiting
        • START Barcelona - HM Nou Delfos Hospital
        • Contact:
          • Phone Number: +34 935 23 05 55
      • Lleida, Spain, 25198
        • Recruiting
        • Hospital Universitari Arnau de Vilanova
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundación Jiménez Díaz
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe
    • Catalonia
      • Barcelona, Catalonia, Spain, 08035
        • Recruiting
        • Hospital Universitario Vall d'Hebron
    • Madrid
      • Madrid, Madrid, Spain, 28007
        • Recruiting
        • Hospital Beata Maria Ana
      • Pozuelo de Alarcón, Madrid, Spain, 28223
        • Recruiting
        • Hospital Quiron Madrid - NEXT Oncology
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles
      • San Diego, California, United States, 92093
        • Recruiting
        • University Of California San Diego Moores Cancer Center
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Simon Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Insitute
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • St. Lukes Hospital of Kansas City
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI Oncology Partners
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75230
        • Recruiting
        • SCRI at Mary Crowley
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
          • Jordi Rodon Ahnert, M.D., PhD
          • Phone Number: 713-792-5603
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas San Antonio (UTSA)
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • Wisconsin Institute for Medical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: BBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
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.
Drug: BBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
Drug: Trastuzumab
Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days
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.
Drug: BBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
Drug: Fulvestrant
Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
Drug: Ribociclib
Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
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.
Drug: BBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
Drug: Fulvestrant
Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
Drug: Ribociclib
Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
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.
Drug: BBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
Drug: FOLFOX
Patients will receive FOLFOX as infusion every 14 days
Drug: Bevacizumab
Patients will receive bevacizumab as infusion every 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
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
Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: Up to approximately 5 years
Up to approximately 5 years
Clinical benefit rate (CBR) as assessed by RECIST v1.1.
Time Frame: Up to approximately 5 years
Up to approximately 5 years
Duration of response (DOR) as assessed by RECIST v1.1.
Time Frame: Up to approximately 5 years
Up to approximately 5 years
Progression-free survival (PFS) as assessed by RECIST v1.1
Time Frame: Up to approximately 5 years
Up to approximately 5 years
Area under the concentration-time curve (AUC
Time Frame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Maximum plasma drug concentration (Cmax)
Time Frame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Time for maximum plasma drug concentration (Tmax)
Time Frame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Objective response rate (ORR) as assessed by RECIST v1.1 for patients with measurable disease
Time Frame: Up to approximately 5 years
Up to approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 29, 2024

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

October 1, 2024

First Submitted That Met QC Criteria

October 1, 2024

First Posted (Actual)

October 3, 2024

Study Record Updates

Last Update Posted (Actual)

September 9, 2026

Last Update Submitted That Met QC Criteria

September 2, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TBBO10203-101
  • 2024-519445-29-00 (Ctis)
  • BREAKER-101 (Other Identifier: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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