This phase II trial tests how well giving CIMAvax-EGF with KRAS G12C inhibitor (sotorasib or adagrasib) for the treatment of patients with KRAS G12C mutated non small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Vaccines, such as CIMAvax-EGF, made from specific peptides or antigens may help the body build an effective immune response to kill tumor cells. Sotorasib and adagrasibare in a class of medications called kinase inhibitors. They work by blocking the signals that cause tumor cells to multiply. This helps to stop the spread of tumor cells. Giving CIMAvax-EGF with a KRAS G12C inhibitor may be effective for treating advanced, KRAS G12C mutated non small cell lung cancer.
PRIMARY OBJECTIVE: I. To identify the 12-month progression free survival (PFS) of patients with advanced stage KRAS G12C mutated non small cell lung cancer (NSCLC) treated with Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine (CIMAvax-EGF) in combination with KRAS G12C inhibitor. SECONDARY OBJECTIVE: I. To assess response rate, 6-month PFS, safety profile and overall survival of patients treated with the combination of CIMAvax-EGF and KRAS G12C inhibitor. OUTLINE: LOADING PHASE: Patients receive CIMAvax-EGF intramuscularly (IM) every 2 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM every 4 weeks for a total of 1 year of treatment, in the absence of disease progression or unacceptable toxicity. Patients who remain on study beyond 12 months and with antibody titer ≥ 1:4000 at the end of the loading phase may receive CIMAvax-EGF IM every 2 months as long as titer levels continue to be maintained \> 1:4000. After the first 6 months of alternate dosing, may receive CIMAvax-EGF IM every 3 months in the absence of disease progression or unacceptable toxicity. Patients also receive sotorasib orally (PO) once daily (QD) or adagrasib PO twice daily (BID) per their physician choice on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) at baseline and as clinically indicated and undergo computed tomography (CT) scan and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 30 days for 120 days then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Given PO
Undergo blood sample collection
Undergo CT scan
Undergo MRI
Given IM
Given PO
Roswell Park Cancer Institute
Buffalo, New York, United States
Progression free survival (PFS)
Will be calculated as the binomial proportion of patients who have not experienced a PFS event within 12 months of study enrollment. The 95% confidence intervals for 12-month PFS will be estimated using Jeffreys method.
Time frame: From enrollment to the loading phase and documentation of disease progression or death, at 12 months
Dose limiting toxicity (Safety lead in)
Time frame: Up to 3 years
Objective response rate (ORR)
Will be based on Response Evaluation Criteria in Solid Tumors. Will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients. The 95% confidence intervals for ORR will be estimated using Jeffreys method.
Time frame: Up to 3 years
Progression free survival (PFS)
Will also be presented using Kaplan-Meier product limit estimators.
Time frame: From enrollment to the loading phase and documentation of disease progression or death, at 6 months
Median PFS
Will also be presented using Kaplan-Meier product limit estimators.
Time frame: From enrollment to the loading phase and documentation of disease progression or death, up to 3 years
Overall survival
Will also be presented using Kaplan-Meier product limit estimators.
Time frame: From study enrollment to the Loading Phase and death from any cause, up to 3 years
Incidence of adverse events (AEs)
The maximum grade for each type of AEs will be recorded for each patient based on National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The frequency of AEs will be tabulated by maximum grade per event across all dose levels and cycles.
Time frame: Up to 3 years
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