Safety & Efficacy Study of EGF Cancer Vaccine to Treat Stage IV Biomarker Positive, Wild Type EGF-R NSCLC Patients

Study Overview
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Brief Summary
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The vaccine contains humanized recombinant antigen (EGF - Epithelial Growth Factor) and an adjuvant. The antibodies induced by vaccination will react with circulating EGF leading to removal of EGF from the circulation. As a result, binding to its target EGF-Receptor is prevented. Blocking of EGF-Receptor is preventing activation and stimulation of proliferation of tumour cell. A Phase 3 clinical trial on the EGF vaccine is ongoing in Cuba. The result from previous studies demonstrated positive correlation between extended survival and immune response against the vaccination in the late-stage NSCLC patients' age below 60 with improved quality of life. The purpose of this international Phase 3 trial is to determine whether the recombinant human EGF cancer vaccine is safe, immunogenic and effective in the treatment of stage IV NSCLC patients who are positive in the selective EGF biomarker and wild type EGF-Receptor compared to standard treatment and supportive care.

Official Title
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Phase 3 Open-label, Multicentre, Randomised Trial to Establish Safety & Efficacy of an EGF Cancer Vaccine in Inoperable, Stage IV Biomarker Positive,Wild Type EGF-R NSCLC Patients Eligible to Receive Standard Treatment and Supportive Care

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Biological: EGF Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are aged 18 or older. Have serum EGF concentration >250 pg/ml determined from sample taken at screening. Have wild type EGF-R sequence. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Have adequate bone marrow, liver and renal function, as assessed by the Investigator. A sample taken at Screening should confirm that: White blood cell (WBC) count ≥ 3000 per µL Platelet count ≥ 100,000 per µL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN when liver metastases are present) Total bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN Have histologically and/or cytologically confirmed diagnosis of NSCLC, corresponding to locally and regionally advanced inoperable disease (Stage IV [as defined by the American Joint Committee on Cancer staging system- TNM 7th edition 2010]) excluding brain metastases. Are eligible to receive first-line chemotherapy (without concurrent radiotherapy to thorax measurable lesions or consolidation radiotherapy). Agree to use double-barrier contraception (males and females alike [if applicable]). A negative pregnancy test must be documented at Screening for females of childbearing potential. Note: Females of childbearing potential are defined as those women with less than 2 years after last menstruation and not surgically sterile, while post-menopausal refers to those women with at least 2 years from last menstruation. Have signed a voluntary written informed consent form (ICF). Patients should be cooperative, willing and able to participate and adhere to the Protocol requirements, including their availability for the follow-up. Exclusion Criteria: Patient has no measurable disease (as defined by RECIST Criteria, version 1.1). Patient has EGF-R mutation. Patient has EGF serum concentration below required threshold. Patient is a candidate for concurrent chemo-radiotherapy or post chemo thoracic radiotherapy. Patient has a history of known or suspected central nervous system (CNS) metastases. Patient has a history of primary malignancy (except resected non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix), unless in complete remission and off all chemotherapy and/or radiotherapy for that disease for a minimum of 5 years. Any palliative radiotherapy to alleviate pain in bone metastases is permitted. Patient is taking immunosuppressant drugs such as azathioprine, tacrolimus, cyclosporine, etc. Use is not permitted within 1 month before Screening. Patient is taking any other immunotherapy. Patient has primary or secondary immunodeficiencies (e.g. documented Human Immunodeficiency Virus [HIV]). Patient has autoimmune disease. Patient has undergone splenectomy. Patient is taking oral, intramuscular or intravenous corticosteroids. Use is not permitted within 1 month before Screening. Inhaled corticosteroids to treat respiratory insufficiency (e.g. chronic obstructive pulmonary disease [COPD]), or topical steroids are permitted. Patient has neurotoxicity (Grade ≥2). Patient has diarrhoea (Grade ≥2). Patient has received other vaccines (with the exception of the influenza vaccine), within 1 month before Screening. Patient has a history of any severe or life-threatening hypersensitivity reaction. Patient has an unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal and metabolic disease). Patient has recent history (within 6 months before Screening) of chronic alcohol or drug abuse which may compromise the patient's safety or ability to participate in study activities. Patient has a history of psychiatric disorder that prevents patients from providing informed consent or following Protocol instructions. Patient is currently enrolled in an investigational device or drug trial, or <1 month since completing an investigational device or drug trial. Female patients who are pregnant or lactating. Patient has any other factor that in the opinion of the Investigator (or designee) would make the patient unsafe or unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGF Vaccine<br>Patients in this arm will receive a low dose of cyclophosphamide and the recombinant human rEGF-P64K/Montanide ISA 51 | Biological: EGF Vaccine<br>* 1.2mL of conjugate-adjuvant mix injection at four sites during the Post First-Line Chemotherapy. Reduced dose of injection at two sites during the Pre-Progression Phase.<br>* Other names: Cyclophosphamide and the recombinant human rEGF-P64K/Montanide ISA 51;|
| No Intervention: Best Supportive Care<br>Patients in this arm will receive best supportive care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | To assess overall survival (OS) of an EGF cancer vaccine in inoperable, stage IV biomarker positive, wild type EGF-R, NSCLC patients compared to the control group receiving best treatment and supportive care. OS is defined as the time from randomisation to death due to any cause. | Each patient will be followed till death occurs within study time frame of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of EGF Cancer Vaccine as assessed by Adverse Events (AEs) | To assess the frequency and number of patients develop AEs, related AEs, serious AEs (SAEs) and AEs leading to withdrawal or death | Each patient will be followed till death occurs within study time frame of 3 years | 
| Progression-Free Survival (PFS) | Progression parameters include radiological or clinical progression, withdrawal due to progression, and death due to any cause. | Each patient will be followed till objective tumour progression or death (whichever occurs first) within time frame of study of 3 years | 
| Survival Rate | To assess the percentage of patients that are alive at 12 months and 24 months in EGF cancer vaccine study group compared to control group. | Each patient will be followed at 12 and 24 months after randomization | 
| Time to Progression (TTP) | To assess Time to Progression (TTP) from the time of randomisation to first documented disease progression of EGF cancer vaccine study group patients compared to control group. | Each patient will be followed till observed tumour progression within study time frame of 3 years | 
| Response Rate (RECIST criteria) | To assess the percentage of patients with a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria Version 1.1. | Each patients will be followed till death occurs within study time frame of 3 years | 
| Safety of EGF Cancer Vaccine by Laboratory Assessment | To assess haematology, biochemistry and urinalysis parameters | Each patients will be followed till death occurs within study time frame of 3 years | 
| Safety of EGF Cancer Vaccine assessed by Vital Signs | To assess systolic and diastolic blood pressure, body temperature and pulse rate | Each patients will be followed till death occurs within study time frame of 3 years | 
| Safety of EGF Cancer Vaccine as assessed by Physical Examination | To assess eyes, neurological and cardiovascular systems, lungs, abdomen, and any other areas with signs and symptoms of disease, and of the head, neck, ears, nose, mouth, throat, thyroid, lymph nodes and extremities | Each patient will be followed till death occurs within study time frame of 3 years | 
| Quality of Life (QoL) | To assess the general physical health of patients with a 36-item, short-form health survey until disease progression | Each patient will be followed till death occurs within study time frame of 3 years |