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

NCT05631249 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 2021-006958-312021/34012024-510837-16-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Sotorasib treatment

EXPERIMENTAL

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

Drug: Sotorasib 120Mg Tab

Interventions

Sotorasib 120Mg Tab DRUG

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

Sotorasib treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (5)

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

AP-HM Hôpital Nord

Marseille, 13015, France

RECRUITING

Hôpital Paris Saint Joseph

Paris, 75014, France

RECRUITING

AP-HP Hôpital Tenon

Paris, 75020, France

NOT YET RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Mihaela ALDEA, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lynda MATI

CONTACT

+33 1 42 11 42 11; Lynda.mati@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: November 30, 2022
• Study Start: December 13, 2022
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2027
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)