KRAS P.G12CPhase 2CODEBREAK-IGRNCT05631249
Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
A Phase 2 study testing Sotorasib 120Mg Tab in people with KRAS P.G12C and Non Small Cell Lung Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 5 sites in France.
Trial summary
This study aims to provide a comprehensive understanding of sotorasib's mechanisms of action and resistance in NSCLC patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- KRAS P.G12C, Non Small Cell Lung Cancer
- What is being tested?
- Sotorasib 120Mg Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 5 sitesFrance
- Study dates
- 13 Dec 2022to 12 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age higher than 18 years;
- ECOG less or equal to 1 at the time of screening;
- Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through molecular testing (results of both tissue and liquid biopsy are accepted);
- Subjects will have progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
- Life expectancy of longer than 3 months from the time of screening, in the opinion of the investigator;
- Patients must have lesions easily accessible to biopsy and must have accepted to perform pre-treatment, on-treatment and end-of-treatment biopsies;
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- Have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to registration
- Patients must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed.
- Patients should be able and willing to comply with study visits and procedures as per protocol.
- Patients must be affiliated to a Social Security System or beneficiary of the same.
Who cannot join
- Patient unwilling to participate to the biological investigations and to perform biopsies and blood sample collection as required in the protocol;
- Use of known cytochrome P450 (CYP) 3A4 or P-gp sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to registration, that was not reviewed and approved by the principal investigator.
- Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives (whichever is longer) prior to registration, that was not reviewed and approved by the principal investigator.
- Inadequate washout period prior to registration, defined as: Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study shorter than 14 days or 5 half-lives;
- Prior treatment with a KRAS inhibitor.
- Major surgery within 28 days of registration.
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- Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to registration, unstable arrhythmias or unstable angina.
- Severe infections within 2 weeks prior to registration, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia. Prophylactic antibiotics are allowed.
- Baseline or unresolved pneumonitis from prior treatment;
- Current CTCAE version 5.0 grade higher or equal to 2 peripheral neuropathy.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Subjects with PleurX catheters in place may be considered for the study with Principal Investigator approval.
- Known history of Human Immunodeficiency Virus (HIV) infection
- 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)
- Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary.
- Undetectable anti-HBs in this setting would suggest unclear and possible infection, and needs exclusion).
- Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible.
- Leptomeningeal disease and active brain metastases. Subjects who have had brain metastases resected or have received whole brain radiation therapy or stereotactic radiosurgery ending at least 2 weeks prior to registration are eligible if they meet all of the following criteria:
- residual neurological symptoms grade less or equal to 2;
- on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and
- follow-up brain imaging performed within 30 days of enrollment shows no progression or new lesions appearing.
- Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 7 days after the last dose of sotorasib or during treatment if planning to become pregnant.
- 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 after the last dose of sotorasib
- Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 7 days after the last dose of sotorasib
- Male subjects unwilling to abstain from donating sperm during treatment and for an additional 7 days after the last dose of investigational product.
- Any evidence of primary malignancy other than locally advanced or metastatic lung cancer at within 3 years of registration, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated;
- Participation in another clinical trial evaluating an experimental drug (except non-interventional research).
- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
- Hypersensitivity to the active substance or to any excipient
- Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
Centre Léon Bérard
Lyon, 69373
Aurélie SWALDUZ, MD, +33 4 69 85 60 41, aurelie.swalduz@lyon.unicancer.fr
Lynda MATI, 0142113730, lynda.mati@gustaveroussy.fr
- Recruiting
AP-HM Hôpital Nord
Marseille, 13015
Pascale TOMASINI, MD, +33 4 91 38 46 44, pascale.tomasini@ap-hm.fr
Lynda MATI, 0142113730, lynda.mati@gustaveroussy.fr
- Recruiting
Hôpital Paris Saint Joseph
Paris, 75014
NALTET Charles, MD, cnaltet@ghpsj.fr
Lynda MATI, 0142113730, lynda.mati@gustaveroussy.fr
- Not yet recruiting
AP-HP Hôpital Tenon
Paris, 75020
Jacques CADRANEL, MD, +33 1 56 01 65 31, jacques.cadranel@aphp.fr
Lynda MATI, 0142113730, lynda.mati@gustaveroussy.fr
- Recruiting
Gustave Roussy
Villejuif, 94800
REMON MASIP Jordi, MD, Jordi.REMON-MASIP@gustaveroussy.fr
Lynda MATI, 0142113730, lynda.mati@gustaveroussy.fr
About this study
Official title: An Interventional and Translational Study Investigating Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
This study aims to provide a comprehensive understanding of sotorasib's mechanisms of action and resistance in NSCLC patients.
- Conditions
- KRAS P.G12C, Non Small Cell Lung Cancer
- Being tested
- Sotorasib 120Mg Tab
- 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.
Sotorasib 120Mg TabDrug
Daily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up
| Study group | Role | What they receive |
|---|---|---|
| Sotorasib treatment | Experimental | Sotorasib : 120 mg, once a day, per os, until progression, unacceptable toxicity, death or lost to follow-up Receives: Drug: Sotorasib 120Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor response assessment
To evaluate tumor response at 4 months and decipher relevant biomarkers associated with primary (progression within the first 4 months) and acquired resistance to sotorasib (progression after 4 months).
Measured: at 4 months after treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start13 Dec 2022
- Primary completion12 Dec 2027 (estimated)
- Study completion12 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KRAS P.G12CStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mihaela ALDEA, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05631249
- Sponsor's protocol ID
- 2021-006958-31
- Other IDs
- 2021/3401, 2024-510837-16-00
- Acronym
- CODEBREAK-IGR
- Status last verified
- May 2025
- First submitted
- 21 Nov 2022
- Last updated
- 8 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Interventional and Translational Study Investigating Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
- ClinicalTrials.gov ID
- NCT05631249
- Acronym / sponsor ID
- CODEBREAK-IGR / 2021-006958-31
- Conditions
- KRAS P.G12C, Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- 13 Dec 2022 (actual)
- Primary completion
- 12 Dec 2027 (estimated)
- Study completion
- 12 Dec 2027 (estimated)
- First posted
- 30 Nov 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.
This study aims to provide a comprehensive understanding of sotorasib's mechanisms of action and resistance in NSCLC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sotorasib treatment | Experimental | Drug: Sotorasib 120Mg TabSotorasib : 120 mg, once a day, per os, until progression, unacceptable toxicity, death or lost to follow-up |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age higher than 18 years;
- ECOG less or equal to 1 at the time of screening;
- Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through molecular testing (results of both tissue and liquid biopsy are accepted);
- Subjects will have progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
- Life expectancy of longer than 3 months from the time of screening, in the opinion of the investigator;
Key exclusion criteria (33 listed)
- Patient unwilling to participate to the biological investigations and to perform biopsies and blood sample collection as required in the protocol;
- Use of known cytochrome P450 (CYP) 3A4 or P-gp sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to registration, that was not reviewed and approved by the principal investigator.
- Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives (whichever is longer) prior to registration, that was not reviewed and approved by the principal investigator.
- Inadequate washout period prior to registration, defined as: Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study shorter than 14 days or 5 half-lives;
- Prior treatment with a KRAS inhibitor.
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 |
|---|---|---|
| Sotorasib 120Mg TabDaily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up | Drug | Sotorasib treatment |
Primary outcome
Tumor response assessment
Time frame: at 4 months after treatment start
To evaluate tumor response at 4 months and decipher relevant biomarkers associated with primary (progression within the first 4 months) and acquired resistance to sotorasib (progression after 4 months).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Individual participant dataSharing planned: No
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Non-Small Cell Lung Cancer, KRAS G12C Lung Cancer
RecruitingPhase 1/2
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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.
Mihaela ALDEA, MD principal investigator
Gustave Roussy, Cancer Campus, Grand Paris
5 sites 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 120Mg Tab in people with KRAS P.G12C and Non Small Cell Lung Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 5 sites in France.
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 10 inclusion and 33 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: looking for participants now, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lynda MATI (+33 1 42 11 42 11 ext. 3730, Lynda.mati@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor response assessment (time frame: at 4 months after treatment start). 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 8 May 2025.