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

Phase 1

Recruiting

• Conditions: 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
• Interventions: Drug: BBO-10203; Drug: Trastuzumab; Drug: Fulvestrant; Drug: FOLFOX; Drug: Ribociclib; Drug: Bevacizumab

• Registration Number: NCT06625775
• Lead Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

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.

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 Timeline

• Study First Submitted: 2024-10-01
• Study First Submitted QC: 2024-10-01
• Study First Posted: 2024-10-03
• Study Start: 2024-10-29
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-17
• Last Update Posted: 2025-06-24
• Primary Completion: 2028-11
• Study Completion: 2028-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 392

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BBO-10203	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.
BBO-10203 + Trastuzumab	BBO-10203	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.
BBO-10203 + Trastuzumab	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.
BBO-10203 + Fulvestrant	BBO-10203	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.
BBO-10203 + Fulvestrant	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.
BBO-10203 + Fulvestrant	Ribociclib	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.
BBO10203 + Fulvestrant + Ribociclib	BBO-10203	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.
BBO10203 + Fulvestrant + Ribociclib	Fulvestrant	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.
BBO10203 + Fulvestrant + Ribociclib	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.
BBO10203 + FOLFOX + Bevacizumab	BBO-10203	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.
BBO10203 + FOLFOX + Bevacizumab	FOLFOX	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.
BBO10203 + FOLFOX + Bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) as assessed by RECIST v1.1	Up to approximately 5 years
Overall survival (OS)	Up to approximately 5 years
Maximum plasma drug concentration (Cmax)	Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Time for maximum plasma drug concentration (Tmax)	Predose (within 30 minutes) of C1D1 until up to approximately 5 years
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
Area under the concentration-time curve (AUC	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	Up to approximately 5 years

Trial Locations

Locations (12)

SCRI at Mary Crowley; 🇺🇸 Dallas, Texas, United States

University of Texas San Antonio (UTSA); 🇺🇸 San Antonio, Texas, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Indiana University Simon Comprehensive Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Insitute; 🇺🇸 Boston, Massachusetts, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Scientia Clinical Research; 🇦🇺 Randwick, New South Wales, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia