Phase II Study of CIMAVAX-EGF in Combination With KRAS G12C Inhibitors as Treatment for Advanced Stage KRAS G12C Mutated NSCLC
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Dose limiting toxicity (Safety lead in)
Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
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)
Arms & Interventions
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.
Intervention: Adagrasib (Drug)
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.
Intervention: Biospecimen Collection (Procedure)
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.
Intervention: Computed Tomography (Procedure)
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.
Intervention: Magnetic Resonance Imaging (Procedure)
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.
Intervention: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine (Biological)
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.
Intervention: Sotorasib (Drug)
Outcomes
Primary Outcomes
Dose limiting toxicity (Safety lead in)
Time Frame: Up to 3 years
Progression free survival (PFS)
Time Frame: From enrollment to the loading phase and documentation of disease progression or death, at 12 months
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.
Secondary Outcomes
- Objective response rate (ORR)(Up to 3 years)
- Progression free survival (PFS)(From enrollment to the loading phase and documentation of disease progression or death, at 6 months)
- Median PFS(From enrollment to the loading phase and documentation of disease progression or death, up to 3 years)
- Overall survival(From study enrollment to the Loading Phase and death from any cause, up to 3 years)
- Incidence of adverse events (AEs)(Up to 3 years)