| Eligibility |
Inclusion Criteria:
1. Age 18 years or older.
2. Histological confirmation of locally advanced or metastatic, non-squamous NSCLC with
an activating EGFR mutation who are not candidates for local curative treatment.
3. Stage IV, according to TNM Version 8, including M1a (malignant effusion) or M1b
(distant metastasis), or locally advanced disease for which there is no curative
treatment (including patients who progress after chemoradiotherapy in Stage III
disease).
4. Centrally confirmed EGFR exon 19 deletion, exon 21 (L858R, L861Q) or exon 18 (G719X)
mutation before treatment (concomitant T790M pre-treatment mutation is permitted).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. Existence of measurable or evaluable disease (according to RECIST 1.1 criteria).
Patients with asymptomatic and stable brain metastases are eligible for the study.
7. Possibility of obtaining tissue samples, via a biopsy or surgical resection of the
primary tumour or metastatic tumour tissue, within 60 days prior to the start of
treatment.
8. Life expectancy =12 weeks.
9. Adequate haematological function, defined as: absolute neutrophil count (ANC) >1.5 x
109/L, platelet count >100.0 x 109/L, and haemoglobin >9.0 g/dL (>6.2 mmol/L).
10. Adequate coagulation, defined as: international normalised ratio (INR) =1.5.
11. Adequate liver function, defined as: total bilirubin <1.5 x upper limit of normal
(ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <2.5 x
ULN, alkaline phosphatase <5 ULN, except in the presence of single bone metastases and
in the absence of any liver disorders.
12. Adequate renal function, defined as: calculated creatinine clearance >50 mL/min
(Cockcroft-Gault formula) and proteinuria <2+ (dipstick).
13. Ability to complete the study, and residing within geographical proximity allowing for
adequate follow-up.
14. Resolution of all acute toxic effects of any previous anti-cancer therapy (which can
only be adjuvant or neoadjuvant) or previous surgical interventions not exceeding
grade =1 according to the National Cancer Institute CTCAE Version 4.0 (except for
alopecia or other side effects that the investigator does not consider to be a risk to
patient safety).
15. All men, and women of childbearing potential, must agree to use a contraception method
during the study treatment period and for at least 12 months after the last dose of
EGF-TKI. Sexually active men, and women of childbearing potential, who are unwilling
to use a contraceptive method are not eligible for the study.
16. Provision of written informed consent, signed and dated by the patient and the
investigator, before any study interventions are performed.
Exclusion Criteria:
1. Locally advanced lung cancer candidate for curative treatment through radical surgery
and/or radiotherapy, or chemotherapy.
2. Diagnosis with another lung cancer subtype, patients with mixed NSCLC with
predominantly squamous cell cancer, or with any small-cell lung cancer component.
3. Presence or history of any other primary malignancy other than NSCLC within 5 years
prior to enrolment into the study. Patients with a history of adequately treated basal
or squamous cell carcinoma of the skin or any adequately treated in situ carcinoma may
be included in the study.
4. Presence of one measurable or evaluable tumour lesion that has been resected or
irradiated prior to enrolment in the study.
5. Receipt of prior antineoplastic treatment for advanced disease.
6. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant
chemotherapy is permitted if at least 6 months have elapsed between the end of
chemotherapy and the first day of EGF-PTI.
7. Previous treatment for lung cancer with an EGFR.
8. Concomitant use of immunosuppressant drugs such as azathioprine, tacrolimus,
cyclosporine, etc. Use is not permitted within 1 month before screening.
9. Concomitant treatment with any other immunotherapy.
10. Receipt of other vaccines (with the exception of the influenza vaccine), within 1
month before screening.
11. Concomitant treatment with 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), or topical
steroids are permitted.
12. Treatment with an investigational drug within 3 weeks before the first dose of
EGF-PTI.
13. Patients of either sex who are unwilling to use an adequate contraception method until
12 months after the last dose of EGF-PTI or EGFR TKI, whichever is later.
14. History of interstitial lung disease induced by drugs, radiation pneumonitis requiring
steroid treatment, or any evidence of clinically active interstitial lung disease.
15. Any of the following ECG abnormalities:
- Corrected QT interval (QTc) >470 msec, obtained from 3 ECGs at rest, using the
QTc value determined according to the clinical screening ECG machine.
- Any clinically significant abnormality in ECG rhythm, conduction or morphology at
rest.
- Any factor that increases the risk of QTc prolongation or risk of irregular
heartbeat or sudden inexplicable death under the age of 40 in first-degree
relatives or any concomitant medications that prolong the QT interval.
16. Uncontrolled, active or symptomatic metastases of the central nervous system (CNS),
carcinomatous meningitis or leptomeningeal disease indicated by known clinical
symptoms, cerebral oedema and/or progressive neoplasia. Patients with a history of CNS
metastasis or compression of the spinal cord are eligible if they have received local
final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained
clinically stable without using anticonvulsants and corticosteroids for a minimum of 4
weeks prior to the first day of EGF-PTI treatment.
17. Patients who have had a surgical procedure unrelated to the study within 7 days prior
to the first administration of EGF-PTI, or a significant traumatic lesion during the 4
weeks prior to starting the first dose of EGF-PTI, patients who have not recovered
from the side effects of any major surgery or patients who might need major surgery
during the course of the study.
18. Pregnant or breastfeeding women. Women of childbearing potential, including women who
had their last menstrual period within the last 2 years, must have a negative serum or
urine pregnancy test in the 7 days prior to the first dose of EGF-PTI.
19. Patients with a serious concomitant systemic disorder (e.g., active infection,
including HIV or heart disease) that is incompatible with the study (in the opinion of
the investigator), history of bleeding diathesis or anticoagulant therapy (the use of
low molecular weight heparin is permitted provided that it is used for prophylaxis).
20. Treatment with any of the prohibited concomitant medications that cannot be stopped
for the duration of trial participation.
21. Any other reason that the investigator deems to be incompatible with the patient's
participation in the study.
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