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

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

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.

Inclusion Criteria:

1. Are aged 18 or older.

2. Have serum EGF concentration >250 pg/ml determined from sample taken at screening.

3. Have wild type EGF-R sequence.

4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. 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

6. 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.

7. Are eligible to receive first-line chemotherapy (without concurrent radiotherapy to thorax measurable lesions or consolidation radiotherapy).

8. 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.

9. 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:

1. Patient has no measurable disease (as defined by RECIST Criteria, version 1.1).
2. Patient has EGF-R mutation.
3. Patient has EGF serum concentration below required threshold.
4. Patient is a candidate for concurrent chemo-radiotherapy or post chemo thoracic radiotherapy.
5. Patient has a history of known or suspected central nervous system (CNS) metastases.
6. 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.
7. Patient is taking immunosuppressant drugs such as azathioprine, tacrolimus, cyclosporine, etc. Use is not permitted within 1 month before Screening.
8. Patient is taking any other immunotherapy.
9. Patient has primary or secondary immunodeficiencies (e.g. documented Human Immunodeficiency Virus [HIV]).
10. Patient has autoimmune disease.
11. Patient has undergone splenectomy.
12. 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.
13. Patient has neurotoxicity (Grade ≥2).
14. Patient has diarrhoea (Grade ≥2).
15. Patient has received other vaccines (with the exception of the influenza vaccine), within 1 month before Screening.
16. Patient has a history of any severe or life-threatening hypersensitivity reaction.
17. 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).
18. 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.
19. Patient has a history of psychiatric disorder that prevents patients from providing informed consent or following Protocol instructions.
20. Patient is currently enrolled in an investigational device or drug trial, or <1 month since completing an investigational device or drug trial.
21. Female patients who are pregnant or lactating.
22. Patient has any other factor that in the opinion of the Investigator (or designee) would make the patient unsafe or unsuitable for the study.