Recruiting
Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors
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.
ClinicalTrials.gov IDNCT06625775
PhasePHASE1
Enrollment392
SponsorTheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Age18 Years
SexALL
Conditions studied
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
About this 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.
Interventions
- 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
- 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)
- Drug: FOLFOX — Patients will receive FOLFOX as infusion every 14 days
- Drug: Bevacizumab — Patients will receive bevacizumab as infusion every 28 days
Primary outcomes
- 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)
Eligibility information
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 locations
- City of Hope Comprehensive Cancer Center, Duarte, California 91010 United States
- University of California Los Angeles, Los Angeles, California 90095 United States
- University of California San Diego Moores Cancer Center, San Diego, California 92093 United States
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94158 United States
- Moffitt Cancer Center, Tampa, Florida 33612 United States
- Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana 46202 United States
- Massachusetts General Hospital, Boston, Massachusetts 02114 United States
- Dana-Farber Cancer Insitute, Boston, Massachusetts 02215 United States
- St. Lukes Hospital of Kansas City, Kansas City, Missouri 64111 United States
- Washington University School of Medicine, St Louis, Missouri 63110 United States
Showing 10 of 44 reported sites. See the official listing for all locations.
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.