CIMAvax-EGF With KRAS G12C Inhibitor for the Treatment of Advanced, KRAS G12C Mutated Non Small Cell Lung Cancer

Phase II Study of CIMAVAX-EGF in Combination With KRAS G12C Inhibitors as Treatment for Advanced Stage KRAS G12C Mutated NSCLC

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.

Inclusion Criteria:

• Age ≥ 18 years old
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study treatment initiation
• Have pathologically (cytology or histology) confirmed diagnosis of NSCLC. Non-small cell carcinoma diagnosis without specific tissue of origin confirmation may be eligible with approval from primary investigator (PI) review
• Must be eligible for treatment with standard of care KRAS G12C inhibitors
• Documented KRAS G12C mutation. Testing will occur by standard of care next generation sequencing (NGS) testing and results will be available in the medical record
• Have at least 6-month life expectancy
• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
• Platelets ≥ 70 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Plasma creatinine ≤ 1.5 x institution upper limit of normal (ULN)
• ALT (alanine aminotransferase) and aspartate aminotransferase (AST) ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present)
• Total plasma bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3 x ULN with direct bilirubin within normal range
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• Participant agrees to provide blood samples at the start of treatment and at multiple times during the study as well as research specimen allocation at the time of standard of care rebiopsy at the time of disease progression

Exclusion Criteria:

• Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug (see exception allowed for #2)

• Previously treated with KRAS G12C inhibitor (exception allowed for patients who started KRAS G12C inhibitor within 4 weeks of study enrollment)

• Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain metastasis. Subjects must have recovered from all radiation related toxicities

• Active/untreated brain metastasis. Whole brain radiation or gamma knife radiosurgery performed less than 2 weeks prior to first administration of study drug. Previously treated brain metastasis allowed as long as not requiring steroids

• Leptomeningeal involvement regardless of treatment status

• Active, clinically serious infections or other serious uncontrolled medical conditions (exception allowed: patients taking prophylactic anti-viral, anti-fungal or antibiotics. Patients on long-term treatment for acid-fast or fungal organisms must have been on stable dosing of ant-infective regimen for at least 4 weeks of uninterrupted treatment and without associated common toxicity criteria (CTC) grade 2 or higher drug-related lab abnormalities within 4 weeks of study enrollment)

• Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery

• Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases, or who have not fully recovered from side effects of such treatment. Steroids for endocrine replacement or receipt of short course of steroids during this preceding 4-week period as supportive medication such as for drug allergy, anti-emetic, etc. is allowed

• Pregnant or nursing female participants

• Patients diagnosed with a secondary invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason ≤ to 6 (under surveillance or treated), early-stage node-negative estrogen receptor (ER) +/ progesterone receptor (PR) + breast cancer with Oncotype Dx score < 25 (adjuvant hormonal therapy allowed)

• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:

  • Myocardial infarction or arterial thromboembolic events within 30 days prior to enrollment or with severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease

• Patient has known hypersensitivity to the components of the study drugs or any analogs