Non Small Cell Lung CancerPhase 2breakthroughNCT05451056
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
A Phase 2 study testing sotorasib in people with Non Small Cell Lung Cancer, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- sotorasib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Aug 2022to Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject or subject's legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
- Age ≥19 years of age
- Histologically or pathologically documented, locally-advanced and unresectable or metastatic NSCLC.
- 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.
- 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.
- Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
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- 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.
- Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy.
- 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.
- Measurable disease per RECIST v1.1 criteria.
- ECOG Performance Status of ≤ 1
- Adequate hematologic laboratory assessments, defined as the following within 28 days prior to start of study therapy:
- Absolute neutrophil count (ANC) ≥ 1500 cells/μl (without granulocyte colony-stimulating factor support within 10 days of laboratory test used to determine eligibility)
- Hemoglobin ≥ 9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Platelet count ≥ 100,000/μl (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Life expectancy of > 3 months, in the opinion of the investigator
- Adequate liver function, defined as the following:
- Aspartate aminotransferase (AST) and, alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN), except if alkaline phosphatase > 2.5 times the ULN, then AST and/or ALT must be ≤ 1.5 times the ULN
- Serum bilirubin ≤ 1.0 x ULN
- International normalized ratio (INR) and activated partial thromboplastin time ≤ 1.5 x ULN
- Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥ 60 mL/min. Cockcroft- Gault formula will be used for creatinine clearance calculation. Twenty-four hour urine collection is not required but is allowed.
- QTc ≤ 470 msec in females and ≤ 450 msec in males (based on average of screening triplicates)
- -Subject should perform 12-lead ECG 3times within 15minutes at intervals of 2-5 minutes after resting in the sitting position for 5minutes.
- Ability to take oral medications and willing to record daily adherence to investigational product
Who cannot join
- 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)
- Active brain metastases. Subjects who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks (or stereotactic radiosurgery ending at least 2 weeks) prior to study day 1 are eligible if they meet all of the following criteria:
- residual neurological symptoms grade ≤ 2;
- on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and
- follow-up MRI performed within 30 days prior to enrollment shows no progression or new lesions appearing.
- Leptomeningeal disease.
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- Exclusion of hepatitis infection based on the following results and/or criteria:
- Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B)
- Subjects with a prior history of HBV proven to be positive for hepatitis B core antibody
- Surface antigen (HBsAg) is negative
- It is suitable if the HBV deoxyribonucleic acid (DNA; viral load) is less than the lower limit of quantitation according to the local test. Subjects positive for HBsAg due to recent vaccination are eligible if their HBV DNA (viral load) is below the lower limit of quantitation according to local testing.
- Malignancy other than NSCLC within 2 years prior to first dose of drug, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal cell carcinoma, cutaneous squamous cell carcinoma, localized prostate cancer treated with curative intent, or ductal carcinoma in situ treated surgically with curative intent).
- Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
- Significant cardiovascular disease, myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina.
- Severe infections within 4 weeks prior to first dose of drug including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia.
- Subjects participating in other clinical trials are excluded.
- Previous treatment with sotorasib or other KRAS G12C inhibitor
- Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 7 days after the last dose of sotorasib.
- Female subjects of childbearing potential with a positive pregnancy test assessed at Screening or day 1 by a serum pregnancy test and/or urine pregnancy test.
- Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 7 days (sotorasib).
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Yonsei University Health System, Severance Hospital
Seoul
Byoung Chul Cho, +82-2228-0880, cbc1971@yuhs.ac
About this study
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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- sotorasib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sotorasibDrug
Sotorasib will be given 960mg daily PO until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| sotorasib | Experimental | Sotorasib will be given 960mg daily PO until disease progression or unacceptable toxicity . Receives: Drug: sotorasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is measured from the date of start of study to the date of death from any cause.
Measured: From date of start of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression-free survival (PFS)
PFS is measured from the date of start of study to the date of disease progression or death from any cause.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Objective response rate (ORR)
It is evaluated by taking CT of the chest and abdomen (including liver and adrenal glands) or MRI.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2022
- Study start1 Aug 2022 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Byoung Chul Cho, Principal investigator, Yonsei University Health System, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05451056
- Sponsor's protocol ID
- 4-2021-1768
- Acronym
- breakthrough
- Status last verified
- Jul 2022
- First submitted
- 5 Jul 2022
- Last updated
- 11 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05451056
- Acronym / sponsor ID
- breakthrough / 4-2021-1768
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 1 Aug 2022 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 11 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sotorasib | Experimental | Drug: sotorasibSotorasib will be given 960mg daily PO until disease progression or unacceptable toxicity . |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subject or subject's legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
- Age ≥19 years of age
- Histologically or pathologically documented, locally-advanced and unresectable or metastatic NSCLC.
- 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.
- 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.
Key exclusion criteria (22 listed)
- 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)
- Active brain metastases. Subjects who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks (or stereotactic radiosurgery ending at least 2 weeks) prior to study day 1 are eligible if they meet all of the following criteria:
- Leptomeningeal disease.
- Exclusion of hepatitis infection based on the following results and/or criteria:
- Malignancy other than NSCLC within 2 years prior to first dose of drug, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal cell carcinoma, cutaneous squamous cell carcinoma, localized prostate cancer treated with curative intent, or ductal carcinoma in situ treated surgically with curative intent).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sotorasibSotorasib will be given 960mg daily PO until disease progression or unacceptable toxicity. | Drug | sotorasib |
Primary outcome
Overall Survival (OS)
Time frame: From date of start of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
OS is measured from the date of start of study to the date of death from any cause.
Progression-free survival (PFS)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
PFS is measured from the date of start of study to the date of disease progression or death from any cause.
Objective response rate (ORR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
It is evaluated by taking CT of the chest and abdomen (including liver and adrenal glands) or MRI.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Byoung Chul Cho principal investigator
Yonsei University Health System, Severance Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sotorasib in people with Non Small Cell Lung Cancer, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Byoung Chul Cho (+82-2228-0880, cbc1971@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: From date of start of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2022.