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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06625775




Registration number
NCT06625775
Ethics application status
Date submitted
1/10/2024
Date registered
3/10/2024
Date last updated
24/06/2025

Titles & IDs
Public title
Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors
Scientific title
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)
Secondary ID [1] 0 0
2024-519445-29-00
Secondary ID [2] 0 0
TBBO10203-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor, Adult 0 0
Metastatic Breast Cancer 0 0
Advanced Breast Cancer 0 0
HER2 Mutation-Related Tumors 0 0
HER2-positive Metastatic Breast Cancer 0 0
KRAS Mutant Metastatic Colorectal Cancer 0 0
Metastatic Lung Cancer 0 0
Metastatic Colorectal Cancer 0 0
Advanced Lung Cancer 0 0
HR-positive, HER2-negative Advanced Breast Cancer 0 0
HER2-positive Advanced Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BBO-10203
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Ribociclib
Treatment: Drugs - FOLFOX
Treatment: Drugs - Bevacizumab

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 (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.

Experimental: 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.

Experimental: 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.

Experimental: 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.


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

Treatment: Drugs: Trastuzumab
Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days

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

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

Treatment: Drugs: FOLFOX
Patients will receive FOLFOX as infusion every 14 days

Treatment: Drugs: Bevacizumab
Patients will receive bevacizumab as infusion every 28 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent
Timepoint [1] 0 0
Up to approximately 5 years
Primary outcome [2] 0 0
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Timepoint [2] 0 0
Up to approximately 5 years
Primary outcome [3] 0 0
Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Clinical benefit rate (CBR) as assessed by RECIST v1.1.
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
Duration of response (DOR) as assessed by RECIST v1.1.
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
Progression-free survival (PFS) as assessed by RECIST v1.1
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Area under the concentration-time curve (AUC
Timepoint [5] 0 0
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Secondary outcome [6] 0 0
Maximum plasma drug concentration (Cmax)
Timepoint [6] 0 0
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Secondary outcome [7] 0 0
Time for maximum plasma drug concentration (Tmax)
Timepoint [7] 0 0
Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Secondary outcome [8] 0 0
Objective response rate (ORR) as assessed by RECIST v1.1 for patients with measurable disease
Timepoint [8] 0 0
Up to approximately 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2028
Actual
Sample size
Target
392
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Scientia Clinical Research - Randwick
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BBOT (BridgeBio Oncology Therapeutics)
Address 0 0
Country 0 0
Phone 0 0
650-391-9740
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06625775