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

NCT ID: NCT06625775

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

392 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-29

Study Completion Date

2028-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

BBO-10203

Intervention Type DRUG

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

BBO-10203 + Trastuzumab

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab (8mg/kg infusion over 90 minutes on Cycle 1 Day 1, 6mg/kg infusion over 30-90 minutes during subsequent cycles or 600mg subcutaneous). This cohort will enroll patients with HER2-positive advanced breast cancer.

Group Type EXPERIMENTAL

BBO-10203

Intervention Type DRUG

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

Trastuzumab

Intervention Type DRUG

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

BBO-10203 + Fulvestrant

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM). This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

Group Type EXPERIMENTAL

BBO-10203

Intervention Type DRUG

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

Fulvestrant

Intervention Type DRUG

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

Ribociclib

Intervention Type DRUG

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

BBO10203 + Fulvestrant + Ribociclib

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM) and ribociclib (600mg orally) as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

Group Type EXPERIMENTAL

BBO-10203

Intervention Type DRUG

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

Fulvestrant

Intervention Type DRUG

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

Ribociclib

Intervention Type DRUG

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

BBO10203 + FOLFOX + Bevacizumab

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2 + 2400 mg/m2) and bevacizumab (5 mg/kg IV). This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.

Group Type EXPERIMENTAL

BBO-10203

Intervention Type DRUG

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

FOLFOX

Intervention Type DRUG

Patients will receive FOLFOX as infusion every 14 days

Bevacizumab

Intervention Type DRUG

Patients will receive bevacizumab as infusion every 28 days

Interventions

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BBO-10203

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

Intervention Type DRUG

Trastuzumab

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

Intervention Type DRUG

Fulvestrant

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

Intervention Type DRUG

Ribociclib

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

Intervention Type DRUG

FOLFOX

Patients will receive FOLFOX as infusion every 14 days

Intervention Type DRUG

Bevacizumab

Patients will receive bevacizumab as infusion every 28 days

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

University of California San Diego Moores Cancer Center

San Diego, California, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Insitute

Boston, Massachusetts, United States

Site Status RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

SCRI at Mary Crowley

Dallas, Texas, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

University of Texas San Antonio (UTSA)

San Antonio, Texas, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Scientia Clinical Research

Randwick, New South Wales, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Australia Spain

Central Contacts

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BBOT (BridgeBio Oncology Therapeutics)

Role: CONTACT

Phone: 650-391-9740

Email: [email protected]

Other Identifiers

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2024-519445-29-00

Identifier Type: CTIS

Identifier Source: secondary_id

BREAKER-101

Identifier Type: OTHER

Identifier Source: secondary_id

TBBO10203-101

Identifier Type: -

Identifier Source: org_study_id