Dysautonomia International

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

Purpose

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.

Conditions

Non-small Cell Lung Cancer
Metastatic Non-Small Cell Lung Cancer
NSCLC
KRAS G12C
Metastatic Lung Cancer
Advanced Lung Carcinoma

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts 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/exclusion criteria may apply

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1a: sequential/parallel, Phase 1b: parallel
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Cohort 1a - Dose Escalation/Dose Finding Monotherapy	Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) as monotherapy	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD
Experimental Cohort 1b - Dose Escalation/Dose Finding Combination Therapy	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)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: Pembrolizumab Patients will receive IV pembrolizumab
Experimental Cohort 2a - Dose Expansion Monotherapy	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) as monotherapy	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD
Experimental Cohort 2b - Dose Expansion Combination Therapy	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: Pembrolizumab Patients will receive IV pembrolizumab
Experimental Cohort 1b Safety Lead-In - Dose Expansion Doublet Combination Therapy	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: BBO-10203 Participants will receive assigned dose of BBO-8520 orally (PO), QD
Experimental Cohort 1b - Dose Expansion Doublet Combination Therapy	Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: BBO-10203 Participants will receive assigned dose of BBO-8520 orally (PO), QD
Experimental Cohort 1b Safety Lead-In - Dose Expansion Triplet Combination Therapy	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)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: Pembrolizumab Patients will receive IV pembrolizumab Drug: BBO-10203 Participants will receive assigned dose of BBO-8520 orally (PO), QD
Experimental Cohort 1b - Dose Expansion Triplet Combination Therapy	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)	Drug: BBO-8520 Participants will receive assigned dose of BBO-8520 orally (PO), QD Drug: Pembrolizumab Patients will receive IV pembrolizumab Drug: BBO-10203 Participants will receive assigned dose of BBO-8520 orally (PO), QD

Recruiting Locations

O'Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama 35233

University of California - San Diego Moores Cancer Center
La Jolla, California 92093

University of California San Francisco
San Francisco, California 94158

UCLA Health - Santa Monica Cancer Care
Santa Monica, California 90404

University of Colorado Cancer Center
Aurora, Colorado 80045

Yale Cancer Center
New Haven, Connecticut 06510

Norwalk Hospital
Norwalk, Connecticut 06850

OSF Saint Francis Medical Center
Peoria, Illinois 61603

University of Kansas Medical Center
Kansas City, Kansas 66205

University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center
Baltimore, Maryland 21201

Henry Ford Cancer - Detroit
Detroit, Michigan 48282

Roswell Park Cancer Institute
Buffalo, New York 14263

Perlmutter Cancer Center - NYU Langone Health
New York, New York 10016

Memorial Sloan Kettering Cancer Center
New York, New York 10065

Cleveland Clinic
Cleveland, Ohio 44195

USOR - Oncology Associates of Oregon, P.C
Eugene, Oregon 97401

SCRI Oncology Partners
Nashville, Tennessee 37203

Oncology Consultants Texas Medical Center
Houston, Texas 77030

USOR - Texas Oncology - (DFW) Waco
Waco, Texas 76710

Huntsman Cancer Institute
Salt Lake City, Utah 84112

NEXT Oncology
Fairfax, Virginia 22031

Fred Hutchinson Cancer Center
Seattle, Washington 98109

Northwest Medical Specialties
Tacoma, Washington 98405

More Details

Status: Recruiting
Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Study Contact

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
650-405-8440
onkoras-101ct.gov@bridgebiooncology.com

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.