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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Advanced Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Sotorasib; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Drug: Adagrasib

Detailed Description

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
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
      • Contact: Grace K. Dy; Phone Number: 716-845-3099; Email: Grace.Dy@RoswellPark.org
      • Principal Investigator: Grace K. Dy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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: Treatment (CIMAvax-EGF and KRAS G12C inhibitor); LOADING PHASE: Patients receive CIMAvax-EGF 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 PO QD or adagrasib PO 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 MRI at baseline and as clinically indicated and undergo CT scan and blood sample collection throughout the study.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Drug: Sotorasib; Given PO; Other Names: AMG 510; Lumakras; AMG-510; AMG510; Lumykras; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Given IM; Other Names: Center of Molecular Immunology (CIMA) Epidermal Growth Factor (EGF) Vaccine; Center of Molecular Immunology Epidermal Growth Factor Vaccine; CimaVax; CIMAvax EGF; CIMAvax Epidermal Growth Factor Vaccine; CimaVax Vaccine; CIMAvax-EGF; Recombinant Human EGF-P64K/Montanide Vaccine; Drug: Adagrasib; Given PO; Other Names: MRTX849; Krazati; KRAS G12C Inhibitor MRTX849; MRTX 849; MRTX-849

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to the loading phase and documentation of disease progression or death, at 12 months
Dose limiting toxicity (Safety lead in)		Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years
Progression free survival (PFS)	Will also be presented using Kaplan-Meier product limit estimators.	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.	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.	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.	Up to 3 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Grace K Dy, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

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; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Spectrum Analysis; Specimen Handling; Magnetic Resonance Spectroscopy; adagrasib; sotorasib; CIMAvax EGF
• Other Study ID Numbers: I-4697425 (Other Identifier: Roswell Park Cancer Institute); NCI-2026-02049 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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