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

Phase 1

Recruiting

• Conditions: Non-small Cell Lung Cancer; Metastatic Non-Small Cell Lung Cancer; NSCLC; KRAS G12C; Metastatic Lung Cancer; Advanced Lung Carcinoma
• Interventions: Drug: BBO-8520; Drug: Pembrolizumab

• Registration Number: NCT06343402
• Lead Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

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 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 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

Study Timeline

• Study First Submitted: 2024-03-22
• Study First Submitted QC: 2024-04-01
• Study First Posted: 2024-04-02
• Study Start: 2024-05-22
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-14
• Last Update Posted: 2025-01-16
• Primary Completion: 2027-08
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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 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/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1a - Dose Escalation/Dose Finding Monotherapy	BBO-8520	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	Pembrolizumab	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 2b - Dose Expansion Combination Therapy	Pembrolizumab	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)
Cohort 1b - Dose Escalation/Dose Finding Combination Therapy	BBO-8520	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	BBO-8520	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) as monotherapy
Cohort 2b - Dose Expansion Combination Therapy	BBO-8520	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities (DLTs)	approximately 3 years	Number of participants with dose limiting toxicities
Adverse Events	approximately 3 years	Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetics (PK) of BBO-8520	approximately 3 years	Half life (T1/2)
To evaluate preliminary antitumor activity of BBO-8520	approximately 3 years	Progression-free survival (PFS) per (RECIST v1.1)
Overall Survival (OS)	approximately 3 years

Trial Locations

Locations (15)

University of California - San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

UCLA Health - Santa Monica Cancer Care; 🇺🇸 Santa Monica, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

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

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

NEXT Oncology; 🇺🇸 Fairfax, Virginia, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Kinghorn Cancer Centre; 🇦🇺 Darlinghurst, New South Wales, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

The Queen Elizabeth Hospital; 🇦🇺 Woodville South, South Australia, Australia

Peninsula & South Eastern Hematology and Oncology Group (PAS); 🇦🇺 Frankston, Victoria, Australia

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