An Interventional and Translational Study investigating Sotorasib in Previously Treated Locally Advanced or Metastatic non-small-cell lung cancer

Phase 1

• Conditions: ocally-advanced and unresectable or metastatic non-small-cell lung cancer with KRAS G12C mutation; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-006958-31-FR
• Lead Sponsor: Gustave Roussy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-11
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

- Age = 18 years;
- ECOG = 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 > 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, defined as:
• Platelet count: =100 000/mm3 or =100 × 109/L (platelet transfusions are not allowed up to 14 days prior to registration to meet eligibility)
• Hemoglobin (Hgb): =9.0 g/dL (transfusion and/or growth factor support is allowed)
• Absolute neutrophil count (ANC): =1500/mm3 or =1.5 × 109/L (use of growth factors is not allowed in the 14 days prior to registration)
• Serum creatinine (SCr): SCr =1.5 times (x) the upper limit of normal (ULN), OR estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation =30 mL/min/1.73 m²
• Liver function: a) 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 ; b) Serum bilirubin =1.0 x ULN (<3 × ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia))
• Serum albumin: =2.5 g/dL
• Prothrombin time (PT) or Prothrombin time international normalized ratio (PT-INR) and activated partial thromboplastin time(aPTT)/partial thromboplastin time (PTT): =1.5 × ULN, except for patients on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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 <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 IV alimentation, or inability to take oral medication
- Significant cardiovascular disease, such as NYHA 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 v5.0 grade = 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 HIV infection
- Exclusion of hepatitis infection based on the following results and/or criteria:
a) Positive HepBsAg (indicative of chronic or recent acute hepatitis B)
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).
c) Positive Hepatitis C virus antibody: Hepatitis C virus RNA by PCR 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:
a) residual neurological symptoms grade = 2
b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and
c) 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 additio

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified