P2.34: Vaxira and CIMAvax-EGF Therapeutic Vaccines Combination in the Advanced NSCLC Treatment: Track: Immunotherapy.

Combining cancer vaccines with different anticancer therapies such as chemotherapy, radiotherapy and other immunotherapeutic agents has had different levels of success. However, the combination of cancer vaccines with different mechanisms of action has not been explored in clinical trials. .The main clinical and immunological results obtained with two different therapeutic vaccines used in advanced non-small-cell lung cancer patients, inducing an immune response against epidermal growth factor (CIMAvax-EGF) and NeuGcGM3 ganglioside (Vaxira) was explore. An exploratory phase I study was conducted to assess the feasibility of combining Vaxira and CIMAvax’EGF vaccines used in advanced NSCLC patients and determine the effect on humoral immune responses. Twenty patients with histological confirmed NSCLC stages IIIB/IV were treated after progression to the standard first line cisplatin /doublet compound therapy according the treatment established in the Oncology Therapeutic Guidelines (NCCN v.04, 2016) .The vaccination schedule consisted in the administration of 1mg of Vaxira by intradermic route. The first 5 doses every 14 days and the rest every 28 days concomitantly CIMAvax- EGF vaccine 0.6 mg by intramuscular route, the first 4 doses every 14 days and the rest every 28 days. Both vaccines were administered until unmanageable toxicity or patients worsening performance status. Humoral immune responses against Racotumomab anti-idiotype Mab, NeuGcGM3, EGF antigen,, EGF serum levels and inhibition binding assay against EGF were measured by standard ELISA assays, induction of cell cytotoxicity in NeuGcGM3 positive expression cell lines by specific NeuGcGM3 antibodies (IgM and IgG) were measured by flow cytometry analyses (FACS).and cell-cytotoxicity assay. The distribution by clinical stage at inclusion was: 9 in stage IIIB, 11 in stage IV all in progression disease. The vaccines combination antitumor responses were evaluated according the RECIST Criteria, and 50% of evaluable patients achieved partial response (PR) after 12 months of vaccination (long lasting anti-tumor response). The 20 patients (ITT) were included in an evaluation of survival (Kaplan Meier estimate), after a follow up of at least 12 months. Median survival was 6, 7 months. The combination was safe. Only mild adverse events, mainly characterized by injections site reactions, were reported. Higher antibody titers against EGF were obtained in comparison with previous CIMAvax-EGF clinical trials. All patients were classified as GAR (good antibody responder). Complete reduction in circulating EGF was obtained 2 months after vaccination. 80% of EGFR phosphorylation inhibition was obtained at month 5. Immunogenicity of racotumomab as well. anti-idiotypic response was significantly higher compared with the maximum titers obtained in previous Vaxira lung cancer trials. The magnitude of anti-Neu GcGM3 antibody response and the capacity to kill ganglioside-positive tumor cell lines were equivalent to the data reported with this vaccine in previous studies. The combination of Vaxira and CIMAvax-EGF vaccines has an acceptable safety profile. The present data suggest that the combination improve the humoral immune response induced by both vaccine and benefit the outcome of first line-refractory advanced NSCLC patients. A Phase II/III vaccine combination clinical trial in NSCLC advanced patients unsuitable to receive first line chemotherapy treatment is ongoing.