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

NCT06625775 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: TBBO10203-1012024-519445-29-00BREAKER-101
• Study Type: interventional
• Target: 392
• Locations: 4 countries
• Sites: 36

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; HER2-positive Advanced Breast Cancer; HER2-positive Metastatic Breast Cancer; Advanced Breast Cancer; HER2 Mutation-Related Tumors; KRAS Mutant Metastatic Colorectal Cancer; Metastatic Lung Cancer; Metastatic Colorectal Cancer; Advanced Lung Cancer; HR-positive, HER2-negative Advanced Breast Cancer

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

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (8)

• Clinical benefit rate (CBR) as assessed by RECIST v1.1.

  Up to approximately 5 years

• Duration of response (DOR) as assessed by RECIST v1.1.

  Up to approximately 5 years

• Progression-free survival (PFS) as assessed by RECIST v1.1

  Up to approximately 5 years

• Overall survival (OS)

  Up to approximately 5 years

• Area under the concentration-time curve (AUC

  Predose (within 30 minutes) of C1D1 until up to approximately 5 years

Study Arms (5)

BBO-10203

EXPERIMENTAL

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

BBO-10203 + Trastuzumab

EXPERIMENTAL

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; Drug: Trastuzumab

BBO-10203 + Fulvestrant

EXPERIMENTAL

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; Drug: Fulvestrant; Drug: Ribociclib

BBO10203 + Fulvestrant + Ribociclib

EXPERIMENTAL

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; Drug: Fulvestrant; Drug: Ribociclib

BBO10203 + FOLFOX + Bevacizumab

EXPERIMENTAL

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; Drug: FOLFOX; Drug: Bevacizumab

Interventions

BBO-10203 DRUG

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

BBO-10203; BBO-10203 + Fulvestrant; BBO-10203 + Trastuzumab; BBO10203 + FOLFOX + Bevacizumab; BBO10203 + Fulvestrant + Ribociclib

Trastuzumab DRUG

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

BBO-10203 + Trastuzumab

Fulvestrant DRUG

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

BBO-10203 + Fulvestrant; BBO10203 + Fulvestrant + Ribociclib

FOLFOX DRUG

Patients will receive FOLFOX as infusion every 14 days

BBO10203 + FOLFOX + Bevacizumab

Bevacizumab DRUG

Patients will receive bevacizumab as infusion every 28 days

BBO10203 + FOLFOX + Bevacizumab

Ribociclib DRUG

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

BBO-10203 + Fulvestrant; BBO10203 + Fulvestrant + Ribociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (36)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California San Diego Moores Cancer Center

San Diego, California, 92037, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Insitute

Boston, Massachusetts, 02215, United States

RECRUITING

St. Lukes Hospital of Kansas City

Kansas City, Missouri, 64111, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

SCRI at Mary Crowley

Dallas, Texas, 75230, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Texas San Antonio (UTSA)

San Antonio, Texas, 78229, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Wisconsin Institute for Medical Research

Madison, Wisconsin, 53792, United States

RECRUITING

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Institut régional du Cancer de Montpellier - Val d'Aurelle

Montpellier, Occitanie, 34298, France

RECRUITING

Institut Curie - René-Huguenin Hospital

Saint-Cloud, Paris, 92210, France

RECRUITING

lnstitut de Cancérologie de l'Ouest - Site Saint-Herblain

Saint-Herblain, Pays de la Loire Region, 44805, France

RECRUITING

Institut Bergonie

Bordeaux, 33000, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Beata Maria Ana

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Quiron Madrid - NEXT Oncology

Pozuelo de Alarcón, Madrid, 28223, Spain

RECRUITING

IOB Institute of Oncology - Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

RECRUITING

START Barcelona - HM Nou Delfos Hospital

Barcelona, 08023, Spain

RECRUITING

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Trastuzumab; Fulvestrant; ribociclib; Folfox protocol; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

BBOT (BridgeBio Oncology Therapeutics)

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2024
• First Posted: October 3, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); FR (6); US (19); ES (9)