Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C

NCT ID: NCT05631249

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-13
• Study Completion Date: 2027-12-12

Brief Summary

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sotorasib treatment

Sotorasib : 120 mg, once a day, per os, until progression, unacceptable toxicity, death or lost to follow-up

Group Type: EXPERIMENTAL

Sotorasib 120Mg Tab

Intervention Type: DRUG

Daily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up

Interventions

Sotorasib 120Mg Tab

Daily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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;
• 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.

Exclusion Criteria

• 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.
• 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:

1. Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B)

2. 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).

3. 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:

1. residual neurological symptoms grade less or equal to 2;

2. on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and

3. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mihaela ALDEA, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Centre Léon Bérard

Lyon, , France

Site Status: RECRUITING

AP-HM Hôpital Nord

Marseille, , France

Site Status: RECRUITING

Hôpital Paris Saint Joseph

Paris, , France

Site Status: RECRUITING

AP-HP Hôpital Tenon

Paris, , France

Site Status: NOT_YET_RECRUITING

Gustave Roussy

Villejuif, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Lynda MATI

Role: CONTACT

Lynda.mati@gustaveroussy.fr

+33 1 42 11 42 11 ext. 3730

Facility Contacts

Aurélie SWALDUZ, MD

Role: primary

aurelie.swalduz@lyon.unicancer.fr

+33 4 69 85 60 41

Lynda MATI

Role: backup

lynda.mati@gustaveroussy.fr

0142113730

Pascale TOMASINI, MD

Role: primary

pascale.tomasini@ap-hm.fr

+33 4 91 38 46 44

Lynda MATI

Role: backup

lynda.mati@gustaveroussy.fr

0142113730

NALTET Charles, MD

Role: primary

cnaltet@ghpsj.fr

Lynda MATI

Role: backup

lynda.mati@gustaveroussy.fr

0142113730

Jacques CADRANEL, MD

Role: primary

jacques.cadranel@aphp.fr

+33 1 56 01 65 31

Lynda MATI

Role: backup

lynda.mati@gustaveroussy.fr

0142113730

REMON MASIP Jordi, MD

Role: primary

Jordi.REMON-MASIP@gustaveroussy.fr

Lynda MATI

Role: backup

lynda.mati@gustaveroussy.fr

0142113730

Other Identifiers

2021/3401

Identifier Type: OTHER

Identifier Source: secondary_id

2024-510837-16-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-006958-31

Identifier Type: -

Identifier Source: org_study_id