Clinical trial NCT06343402: Open-label Study of BBO-8520 in Adult Subjects With KRASG12C Non-small Cell Lung Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Metastatic Non-Small Cell Lung Cancer
NSCLC
KRAS G12C
Metastatic Lung Cancer
Advanced Lung Carcinoma
Lead sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1a: sequential/parallel, Phase 1b: parallel
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: approximately 3 years
measure: Dose-limiting toxicities (DLTs)
timeFrame: approximately 3 years
Secondary outcomes:
measure: To evaluate preliminary antitumor activity of BBO-8520
timeFrame: approximately 3 years
measure: To evaluate preliminary antitumor activity of BBO-8520
timeFrame: approximately 3 years
measure: To evaluate preliminary antitumor activity of BBO-8520
timeFrame: approximately 3 years
measure: Overall Survival (OS)
timeFrame: approximately 3 years
measure: To characterize the pharmacokinetics (PK) of BBO-8520
timeFrame: approximately 3 years
measure: To characterize the pharmacokinetics (PK) of BBO-8520
timeFrame: approximately 3 years
measure: To characterize the pharmacokinetics (PK) of BBO-8520
timeFrame: approximately 3 years
measure: To characterize the pharmacokinetics (PK) of BBO-8520
timeFrame: approximately 3 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California - San Diego Moores Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Health - Santa Monica Cancer Care
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Hematology and Oncology Group (PAS)
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
References: