Advanced Breast Cancer, Advanced Lung Cancer, HER2 Mutation-Related Tumors, HER2-positive Advanced Breast Cancer, HER2-positive Metastatic Breast Cancer, HR-positive, HER2-negative Advanced Breast Cancer, KRAS Mutant Metastatic Colorectal Cancer, Metastatic Breast Cancer, Metastatic Colorectal Cancer, Metastatic Lung Cancer, Solid Tumor, Adult
Conditions
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
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.
Interventions
DRUGBBO-10203
Participants will receive assigned dose of BBO-10203 orally once daily
DRUGTrastuzumab
Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days
DRUGFulvestrant
Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
DRUGRibociclib
Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
DRUGFOLFOX
Patients will receive FOLFOX as infusion every 14 days
DRUGBevacizumab
Patients will receive bevacizumab as infusion every 28 days
Sponsors
TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Objective response rate (ORR) as assessed by RECIST v1.1 for patients with measurable disease | Up to approximately 5 years |
Countries
Australia, Brazil, France, South Korea, Spain, United States
Contacts
CONTACTBBOT (BridgeBio Oncology Therapeutics)
Outcome results
None listed