BBO-10203

DEVELOPMENT STEP phase-1

SPONSOR MATRIX BridgeBio Oncology Therapeutics [BBOT]

MECHANISM TARGET PI3Kα

[THERAPEUTIC_PROFILE]

Target Indications

Metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant colorectal cancer, KRAS mutant NSCLC

Mechanism Abstract

BBO-10203 is a potent inhibitor of PI3Kα and KRASG12C, selectively and covalently binding to Cys242 in the RAS-Binding Domain of PI3Kα, and inhibiting both the GTP-bound and GDP-bound states of KRASG12C with an IC50 of 0.031 nM and an EC50 of 0.02 nM. BBO-10203 disrupts the interaction between RAS isoforms and PI3Kα, leading to the inhibition of RAS-mediated PI3Kα activation, and reduces pERK expression, cell growth, and induces G1 arrest and apoptosis. BBO-10203 can be used for the research of breast cancer, colorectal cancer, and non-small cell lung cancer.

[3D_INTERACTIVE_CONFORMATION]

PUBCHEM CID: 169134691

INTERACTIVE_3D_CONFORMATION

     INITIALIZING_STRUCTURAL_BIOMATRIX... 

[CLINICAL_TRIALS_REGISTRY]

TOTAL EXTRACTED3

RECRUITING STATUS3

COMPLETED RUNS0

REGISTRY & PHASE

TESTED CONDITION

STUDY TITLE & LIFECYCLE TIMELINES

STATUS

➔

P-1NCT06343402

Non-small Cell Lung CancerMetastatic Non-Small Cell Lung Cancer+4 more

N=350Est. Finish: 2031-09

Open-label Study of BBO-8520 in Adult Subjects With KRASG12C Non-small Cell Lung Cancer

recruiting

ENROLLMENT PATIENT CAPACITY350 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2024-05-22(actual)

Primary End:2031-04(estimated)

Study Finish:2031-09(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-8520 in Subjects With Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - The ONKORAS-101 Study

[INVESTIGATORS_&_FACILITY_ROSTER]

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

[PRIMARY_SUCCESS_ENDPOINTS]

Adverse Events

Analysis Window: approximately 3 years

Dose-limiting toxicities (DLTs)

Analysis Window: approximately 3 years

[SECONDARY_SUCCESS_ENDPOINTS]

To evaluate preliminary antitumor activity of BBO-8520

Analysis Window: approximately 3 years

To evaluate preliminary antitumor activity of BBO-8520

Analysis Window: approximately 3 years

To evaluate preliminary antitumor activity of BBO-8520

Analysis Window: approximately 3 years

Overall Survival (OS)

Analysis Window: approximately 3 years

To characterize the pharmacokinetics (PK) of BBO-8520

Analysis Window: approximately 3 years

To characterize the pharmacokinetics (PK) of BBO-8520

Analysis Window: approximately 3 years

To characterize the pharmacokinetics (PK) of BBO-8520

Analysis Window: approximately 3 years

To characterize the pharmacokinetics (PK) of BBO-8520

Analysis Window: approximately 3 years

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Cohort 1a - Dose Escalation/Dose Finding Monotherapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) as monotherapy

Cohort 1b - Dose Escalation/Dose Finding Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) in combination with pembrolizumab infusion (IV)

Cohort 2a - Dose Expansion Monotherapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) as monotherapy

Cohort 2b - Dose Expansion Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)

Cohort 1b Safety Lead-In - Dose Expansion Doublet Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)

Cohort 1b - Dose Expansion Doublet Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)

Cohort 1b Safety Lead-In - Dose Expansion Triplet Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)

Cohort 1b - Dose Expansion Triplet Combination Therapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)

[DOSING_&_INTERVENTION_SPECIFICITIES]

BBO-8520DRUG

Participants will receive assigned dose of BBO-8520 orally (PO), QD

PembrolizumabDRUG

Patients will receive IV pembrolizumab

BBO-10203DRUG

Participants will receive assigned dose of BBO-8520 orally (PO), QD

➔

P-1NCT06625775

Solid Tumor, AdultMetastatic Breast Cancer+9 more

N=392Est. Finish: 2028-11

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

recruiting

ENROLLMENT PATIENT CAPACITY392 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2024-10-29(actual)

Primary End:2028-11(estimated)

Study Finish:2028-11(estimated)

OFFICIAL PROTOCOL 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)

[INVESTIGATORS_&_FACILITY_ROSTER]

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

[PRIMARY_SUCCESS_ENDPOINTS]

Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent

Analysis Window: Up to approximately 5 years

Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

Analysis Window: Up to approximately 5 years

Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab

Analysis Window: Up to approximately 5 years

[SECONDARY_SUCCESS_ENDPOINTS]

Clinical benefit rate (CBR) as assessed by RECIST v1.1.

Analysis Window: Up to approximately 5 years

Duration of response (DOR) as assessed by RECIST v1.1.

Analysis Window: Up to approximately 5 years

Progression-free survival (PFS) as assessed by RECIST v1.1

Analysis Window: Up to approximately 5 years

Overall survival (OS)

Analysis Window: Up to approximately 5 years

Area under the concentration-time curve (AUC

Analysis Window: Predose (within 30 minutes) of C1D1 until up to approximately 5 years

Maximum plasma drug concentration (Cmax)

Analysis Window: Predose (within 30 minutes) of C1D1 until up to approximately 5 years

Time for maximum plasma drug concentration (Tmax)

Analysis Window: 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

Analysis Window: Up to approximately 5 years

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

BBO-10203

EXPERIMENTAL

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

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab. This cohort will enroll patients with HER2-positive advanced breast cancer.

BBO-10203 + Fulvestrant

EXPERIMENTAL

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

BBO10203 + Fulvestrant + Ribociclib

EXPERIMENTAL

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

BBO10203 + FOLFOX + Bevacizumab

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.

[DOSING_&_INTERVENTION_SPECIFICITIES]

BBO-10203DRUG

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

TrastuzumabDRUG

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

FulvestrantDRUG

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

RibociclibDRUG

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

FOLFOXDRUG

Patients will receive FOLFOX as infusion every 14 days

BevacizumabDRUG

Patients will receive bevacizumab as infusion every 28 days

➔

P-1NCT06917079

Non-Small Cell Lung CancerNSCLC+12 more

N=665Est. Finish: 2029-09

BBO-11818 in Adult Subjects With KRAS Mutant Cancer

recruiting

ENROLLMENT PATIENT CAPACITY665 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2025-03-31(actual)

Primary End:2027-08(estimated)

Study Finish:2029-09(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-11818 in Subjects With Advanced KRAS Mutant Cancers

[INVESTIGATORS_&_FACILITY_ROSTER]

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

[PRIMARY_SUCCESS_ENDPOINTS]

Incidence and severity of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)