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An Open-label, Phase 2trial of Sotorasib in KRAS G12C-mutant Non-small-cell Lung Cancer(NSCLC) Patients and a Translational Study to Find Acquired Resistance Mechanism to Sotorasib | Clinical Trials | Clareo Health

UNKNOWNPHASE2

An Open-label, Phase 2trial of Sotorasib in KRAS G12C-mutant Non-small-cell Lung Cancer(NSCLC) Patients and a Translational Study to Find Acquired Resistance Mechanism to Sotorasib

NCT05451056•Yonsei University

View on ClinicalTrials.gov

Summary

Lung cancer is the most common type of cancer occurring in both males and females worldwide (WHO statistics, 2018), and the 5-year survival rate for advanced NSCLC is low (between 6% and 33%, depending on the stage. The rat sarcoma (RAS) proto-oncogene has been identified as an oncogenic driver of tumorigenesis in several cancers, including NSCLC. The RAS proteins can be mutationally activated at codons 12, 13, or 61, leading to human cancers. Different tumor types are associated with mutations in certain isoforms of RAS, with Kirsten rat sarcoma viral oncogene homolog (KRAS) being the most frequently mutated isoform in most cancers. While the role of KRAS mutations in human cancers has been known for decades, no anti-cancer therapies specifically targeting KRAS mutations have been successfully developed, largely because the protein has been intractable for inhibition by small molecules. AMG 510 is a small molecule that specifically and irreversibly inhibits the KRAS G12C mutated protein. Nonclinical studies of AMG 510 have demonstrated inhibition of growth and regression of cells and tumors harboring KRAS p.G12C, and in clinical Study 20170543, AMG 510 demonstrated antitumor activity in KRAS p.G12C mutated NSCLC. These data suggest that inhibition of KRAS G12C may have therapeutic benefit for subjects with KRAS p.G12C driven cancers. Recently development of liquid biopsy technology has enabled detection of KRAS-driven cancer with plasma ctDNA analysis. Therefore, in this study, we aim to conduct a phase 2 trial of sotorasib in KRAS G12C mutant-patients, and conduct pre-treatment and post-treatment biopsies using tissue and liquid to identify novel mechanisms of acquired resistance to sotorasib in these patients. Total sample size is 37 patients, Sotorasib will be given 960mg daily until disease progression or unacceptable toxicity.

Eligibility

Age

19 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Subject or subject's legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
•2. Age ≥19 years of age
•3. Histologically or pathologically documented, locally-advanced and unresectable or metastatic NSCLC.
•4. have documentation of KRAS p.G12C mutation confirmed by local testing through the current protocol or have documentation of KRAS p.G12C mutation prior to enrollment.
•5. Subjects will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
•6. Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
•7. In locally advanced and unresectable NSCLC, disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation and systemic therapy, the entire treatment course counts as one line of therapy.
•8. Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy.
•9. Subjects must have archived tumor tissue samples (formalin fixed, paraffin embedded \[FFPE\] sample \[FFPE of excisional, core needle, or fine needle aspirate\] collected within 5 years) or be willing to undergo pre-treatment b iopsy (excisional, core needle, or fine needle aspirate) for tissue prior to enrollment.
•10. Measurable disease per RECIST v1.1 criteria.
+33 more criteria

Exclusion Criteria

•1. Previously identified driver mutation (according to local standard of care or guidelines) other than KRAS p.G12C for which an approved therapy is available (including EGFR, ALK, ROS1, BRAF etc)

Locations (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Key Dates

Start Date

August 1, 2022

Primary Completion Date

January 1, 2026

Completion Date

February 1, 2026

Last Updated

July 11, 2022

Enrollment

ESTIMATED participants

Conditions

Non Small Cell Lung Cancer

Interventions

sotorasib

DRUG

Contacts

Byoung Chul Cho

CONTACT

+82-2228-0880 cbc1971@yuhs.ac

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 11, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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An Open-label, Phase 2trial of Sotorasib in KRAS G12C-mutant Non-small-cell Lung Cancer(NSCLC) Patients and a Translational Study to Find Acquired Resistance Mechanism to Sotorasib

Inclusion Criteria

Exclusion Criteria

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