EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard therapies used in the treatment of advanced colorectal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Colo-rectal Cancer
• Intervention / Treatment: Procedure: Computed Tomography; Biological: Bevacizumab; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Irinotecan; Biological: Cetuximab; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Procedure: Metastasectomy; Procedure: Biospecimen collection; Biological: Panitumumbab

Detailed Description

Primary Objective

- Determine the immunogenicity of CIMAvax in patients with metastatic, KRAS/NRAS/BRAF wild type CRC in combination with Chemotherapy plus appropriate biologic agent in 1st or 2nd/3rd line setting and chemotherapy plus anti-EGFR therapy in 2nd/3rd line setting.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy).

  • Cohort A: May have received 1 cycle of chemotherapy± appropriate biologic agent pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will receive the addition of CIMAvax + Bevacizumab or CIMAvax+ anti-EGFR therapy in their second cycle.
  • Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease
  • Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for metastatic disease resistant resection (one cycle of standard chemotherapy with or without appropriate biologic agent is allowed)
• KRAS/NRAS/BRAF wild-type.
• Have an ECOG Performance Status of 0-2

• Patients must have adequate organ and marrow function as defined below:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 75 x 10^9/L
  • Hemoglobin ≥ 8 g/dL
  • Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation)
  • ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present
  • Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range
• Have measurable disease per RECIST 1.1 criteria present.
• 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 paired-tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C)

Exclusion Criteria:

• Toxicity ≥Grade 2 from prior chemotherapy with exception to Grade 2 peripheral neuropathy..
• Other cancer requiring active treatment.
• Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment is exclusionary to Cohort A and C only
• Participants with Her2 positive mutational status
• Had major surgery within 4 weeks 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.
• Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease). Testing is not mandatory.
• Participants with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements.

• 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 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease
  • History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline
  • Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention).
  • History of myocarditis of any etiology
  • History of ventricular arrhythmias
• Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition.
• Pregnant or nursing female participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort C; Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.	Biological: Bevacizumab; Given IV; Drug: Leucovorin; Given IV; Biological: Cetuximab; Given IV; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Given IM; Other Names: CIMAvax EGF; Cimavax; Epidermal Growth Factor (EGF) Vaccine; Procedure: Metastasectomy; Undergo metastasectomy; Procedure: Biospecimen collection; Undergo collection of blood samples
Experimental: Cohort A; LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.	Procedure: Computed Tomography; Undergo CT; Other Names: CAT; CAT SCAN; Biological: Bevacizumab; Given IV; Drug: Fluorouracil; Given IV; Drug: Leucovorin; Given IV; Drug: Oxaliplatin; Given IV; Drug: Irinotecan; Given IV; Biological: Cetuximab; Given IV; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Given IM; Other Names: CIMAvax EGF; Cimavax; Epidermal Growth Factor (EGF) Vaccine; Procedure: Biospecimen collection; Undergo collection of blood samples; Biological: Panitumumbab; Given IV; Other Names: ABX-EGF; ABX-EGF Monoclonal Antibody
Experimental: Cohort B; LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.	Procedure: Computed Tomography; Undergo CT; Other Names: CAT; CAT SCAN; Biological: Bevacizumab; Given IV; Drug: Fluorouracil; Given IV; Drug: Leucovorin; Given IV; Drug: Oxaliplatin; Given IV; Drug: Irinotecan; Given IV; Biological: Cetuximab; Given IV; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine; Given IM; Other Names: CIMAvax EGF; Cimavax; Epidermal Growth Factor (EGF) Vaccine; Procedure: Biospecimen collection; Undergo collection of blood samples; Biological: Panitumumbab; Given IV; Other Names: ABX-EGF; ABX-EGF Monoclonal Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogencity of vaccine	Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method	up to 60 days after last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	time from treatment until disease progression, death or last follow up assesed up to 2 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Anuradha Krishnamurthy, MBBS, Roswell Park Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Actual): February 5, 2026
• Study Completion (Estimated): December 4, 2026

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Surgical Procedures, Operative; Biological Factors; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Intercellular Signaling Peptides and Proteins; Coenzymes; Biological Products; Complex Mixtures; Gastrointestinal Hormones; EGF Family of Proteins; Oxaliplatin; Bevacizumab; Irinotecan; Panitumumab; Cetuximab; Fluorouracil; Leucovorin; Vaccines; Metastasectomy; CIMAvax EGF; Epidermal Growth Factor
• Other Study ID Numbers: I 1578122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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