Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C (CODEBREAK-IGR)

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer; KRAS P.G12C
• Intervention / Treatment: Drug: Sotorasib 120Mg Tab

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lynda MATI; Phone Number: 3730 +33 1 42 11 42 11; Email: Lynda.mati@gustaveroussy.fr

Study Locations

• France
  • Lyon, France, 69373
    • Recruiting
    • Centre Léon Bérard
    • Contact: Aurélie SWALDUZ, MD; Phone Number: +33 4 69 85 60 41; Email: aurelie.swalduz@lyon.unicancer.fr
    • Contact: Lynda MATI; Phone Number: 0142113730; Email: lynda.mati@gustaveroussy.fr
  • Marseille, France, 13015
    • Recruiting
    • AP-HM Hopital Nord
    • Contact: Pascale TOMASINI, MD; Phone Number: +33 4 91 38 46 44; Email: pascale.tomasini@ap-hm.fr
    • Contact: Lynda MATI; Phone Number: 0142113730; Email: lynda.mati@gustaveroussy.fr
  • Paris, France, 75020
    • Not yet recruiting
    • AP-HP Hopital Tenon
    • Contact: Jacques CADRANEL, MD; Phone Number: +33 1 56 01 65 31; Email: jacques.cadranel@aphp.fr
    • Contact: Lynda MATI; Phone Number: 0142113730; Email: lynda.mati@gustaveroussy.fr
  • Paris, France, 75014
    • Recruiting
    • Hôpital Paris Saint Joseph
    • Contact: Lynda MATI; Phone Number: 0142113730; Email: lynda.mati@gustaveroussy.fr
    • Contact: NALTET Charles, MD; Email: cnaltet@ghpsj.fr
  • Villejuif, France, 94800
    • Recruiting
    • Gustave Roussy
    • Contact: Lynda MATI; Phone Number: 0142113730; Email: lynda.mati@gustaveroussy.fr
    • Contact: REMON MASIP Jordi, MD; Email: Jordi.REMON-MASIP@gustaveroussy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotorasib treatment; Sotorasib : 120 mg, once a day, per os, until progression, unacceptable toxicity, death or lost to follow-up	Drug: Sotorasib 120Mg Tab; Daily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	at 4 months after treatment start

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Investigators: Principal Investigator: Mihaela ALDEA, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2027

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Sotorasib
• Other Study ID Numbers: 2021-006958-31; 2021/3401 (Other Identifier: CSET number); 2024-510837-16-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes