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A. Cardona Zorrilla
Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
198TiP - Afatinib plus EGF pathway targeting immunization (EGF-PTI) as first line therapy for EGFR mutant NSCLC: The EPICAL study (ID 332)
12:30 - 13:00 | Author(s): A. Cardona Zorrilla
EGF-PTI elicits an antibody response against EGF and suppresses EGFR signaling. It is a vaccine with autologous humanized recombinant EGF conjugated with recombinant P64K protein of Neisseria meningitides. We previously showed signal transducer and activator of transcription 3 (STAT3) activation as a mechanism of innate resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR mutant (EGFR+) NSCLC1,2. Anti-EGF antibodies block STAT3 activation in EGFR+ cells alone and in combination with EGFR TKIs. They also delay the emergence of resistance to afatinib in vitro3. Sera from patients immunized with EGF-PTI block the EGF-induced EGFR and ERK phosphorylation in serum starved cells. Based on the above data we designed the first phase Ib study to evaluate the safety and efficacy of afatinib plus EGF-PTI as 1st line therapy for metastatic EGFR+ NSCLC patients (NTC….).
This is a multicenter open-label exploratory phase Ib clinical study in Spain and Colombia. Thirty metastatic EGFR+ NSCLC patients will receive treatment with afatinib 40 mg daily plus EGF PTI. EGF PTI will be administered (4 injections, 4.8 mL) on day 1, 14, 28, 43 and 92 (immunization phase) and every 3 months (2 injections, 2.4 mL) (maintenance phase). Treatment will continue until disease progression, intolerable adverse events, consent withdrawal or noncompliance with the study protocol. The primary objective of the study is to evaluate the safety and tolerability of the combination. Secondary objectives include overall response rate, progression free survival, overall survival, time to treatment failure, duration of response and disease control rate. A pre-specified secondary objective of the study is to unravel the molecular mechanisms underlying the potential efficacy of afatinib plus EGF-PTI. To this end, EGFR, ERK, AKT and STAT3 phosphorylation levels will be longitudinally evaluated in EGF-stimulated serum starved cells treated with sera from the patients. Longitudinal blood analyses of EGFR mutations and the expression of a panel of possible predictive biomarkers in the baseline tissue will be also performed.
Clinical trial identification:
EudraCT number: 2017-003237-28
Legal entity responsible for the study:
All authors have declared no conflicts of interest.
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