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

May 4, 2026 updated by: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

350

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Recruiting
        • Kinghorn Cancer Centre
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Recruiting
        • Flinders Medical Centre
      • Woodville South, South Australia, Australia, 5011
        • Recruiting
        • The Queen Elizabeth Hospital
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Recruiting
        • Peninsula & South Eastern Hematology and Oncology Group (PAS)
      • Melbourne, Victoria, Australia, 3051
        • Recruiting
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Linear Clinical Research
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Recruiting
        • Juravinski Cancer Centre
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • The Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Jewish General Hospital
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Rigshospitalet
  • Spain
      • Barcelona, Spain, 08023
        • Recruiting
        • START Barcelona - Hospital HM Nou Delfos
      • Madrid, Spain, 28223
        • Recruiting
        • Hospital Universitario Quironsalud Madrid
      • Madrid, Spain, 28040
        • Recruiting
        • START Madrid - Hospital Universitario Fundacion Jimenez Diaz
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • O'Neal Comprehensive Cancer Center at UAB
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University Of California - San Diego Moores Cancer Center
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California San Francisco
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA Health - Santa Monica Cancer Care
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
      • Norwalk, Connecticut, United States, 06850
        • Recruiting
        • Norwalk Hospital
    • Illinois
      • Peoria, Illinois, United States, 61603
        • Recruiting
        • OSF Saint Francis Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48282
        • Recruiting
        • Henry Ford Cancer - Detroit
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Recruiting
        • Perlmutter Cancer Center - NYU Langone Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • USOR - Oncology Associates of Oregon, P.C
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Scri Oncology Partners
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Oncology Consultants Texas Medical Center
      • Waco, Texas, United States, 76710
        • Recruiting
        • USOR - Texas Oncology - (DFW) Waco
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Oncology
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Northwest Medical Specialties

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: approximately 3 years
approximately 3 years
To evaluate preliminary antitumor activity of BBO-8520
Time Frame: approximately 3 years
Progression-free survival (PFS) per (RECIST v1.1)
approximately 3 years
To characterize the pharmacokinetics (PK) of BBO-8520
Time Frame: approximately 3 years
Area under the curve (AUC)
approximately 3 years
To characterize the pharmacokinetics (PK) of BBO-8520
Time Frame: approximately 3 years
Peak plasma drug concentration (Cmax)
approximately 3 years
To characterize the pharmacokinetics (PK) of BBO-8520
Time Frame: approximately 3 years
Time to Cmax (Tmax)
approximately 3 years
To characterize the pharmacokinetics (PK) of BBO-8520
Time Frame: approximately 3 years
Half life (T1/2)
approximately 3 years
To evaluate preliminary antitumor activity of BBO-8520
Time Frame: approximately 3 years
Objective response rate (ORR) per (RECIST v1.1)
approximately 3 years
To evaluate preliminary antitumor activity of BBO-8520
Time Frame: approximately 3 years
Duration of Response (DOR) per (RECIST v1.1)
approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 2024

Primary Completion (Estimated)

April 1, 2031

Study Completion (Estimated)

September 1, 2031

Study Registration Dates

First Submitted

March 22, 2024

First Submitted That Met QC Criteria

April 1, 2024

First Posted (Actual)

April 2, 2024

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TBBO8520-101
  • ONKORAS-101 (Other Identifier: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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