Advanced Lung Carcinoma, KRAS G12C, Metastatic Lung Cancer, Metastatic Non-Small Cell Lung Cancer, Non-small Cell Lung Cancer, NSCLC
Conditions
Brief summary
A first in human study to evaluate the safety and preliminary antitumor activity of BBO-8520, a KRAS G12C (ON and OFF) inhibitor, as a single agent and in combination with pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation.
Detailed description
This is an open-label, multi-center, Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BBO-8520, a direct inhibitor of KRASG12C (ON and OFF), alone and in combination with the ICI pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation. The study includes dose escalation phase and dose expansion phase
Interventions
DRUGBBO-8520
Participants will receive assigned dose of BBO-8520 orally (PO), QD
DRUGPembrolizumab
Patients will receive IV pembrolizumab
DRUGBBO-10203
Participants will receive assigned dose of BBO-8520 orally (PO), QD
Sponsors
TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1a: sequential/parallel, Phase 1b: parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS G12C mutation * Measurable disease by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Exclusion criteria
* Patients with malignancy within the last 2 years as specified in the protocol * Patients with untreated or unstable brain metastases * Patients with known hypersensitivity to BBO-8520 or its excipients * For Cohorts 1b and 2b: * Patients with a known hypersensitivity to pembrolizumab or its excipients * Patients with active autoimmune disease of history of autoimmune disease that might recur * Patients with a history of interstitial lung disease/pneumonitis that required steroids, or current interstitial lung disease/pneumonitis Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | approximately 3 years | Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) |
| Dose-limiting toxicities (DLTs) | approximately 3 years | Number of participants with dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate preliminary antitumor activity of BBO-8520 | approximately 3 years | Objective response rate (ORR) per (RECIST v1.1) |
| Overall Survival (OS) | approximately 3 years | — |
| To characterize the pharmacokinetics (PK) of BBO-8520 | approximately 3 years | Area under the curve (AUC) |
Countries
Australia, Canada, Denmark, Spain, United States
Contacts
CONTACTTheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Outcome results
None listed