Randomized double blind phase IIb trial in advanced NSCLC patients who did not progress after first line platinum based chemotherapy: Vx-001, a therapeutic cancer vaccine, vs placebo as maintenance therapy
Authors: C. Gridelli, T. Ciuleanu, M. Domine Gomez, A. Szczesna, I. Bover, M. Cobo Dols, N. Kentepozidis, S. Viteri, C. Manegold, D. Khayat, J-Y. Douillard, K. Kosmatopoulos, V. Georgoulias
Journal: Annals of Oncology (2017)

Background: Vx-001 is a a therapeutic cancer vaccine with TERT (telomerase reverse transcriptase) antigen as target. Methods: We tested the Vx-001 vaccine as maintenance therapy in a randomized double blind phase IIb trial in advanced NSCLC patients who did not progress after first line platinum based chemotherapy. Enrolled patients should be HLA-A 0201 positive and their tumor should express TERT. Overall survival (OS) was the primary endpoint of the study. Results: 1407 patients were screened and 221 were randomized. 190 patients (101 placebo and 89 Vx-001 treated) were analysed with no statistically significant in terms of OS beetwen arms. Interestingly there was a strong correlation between vaccine induced immune response and clinical outcome. OS was much longer in the 29% of patients who developed a Vx-001 specific immune response (21.3 months for immune responders vs 13.4 months for non-immune responders p = 0.004). 27% of enrolled patients had a natural immunity against several universal tumor antigens detected at baseline before vaccination suggesting that these patients should have strongly immunogenic tumors. Analysis of OS in this patient population with immunogenic tumors did not show any benefit in Vx-001 treated patients. Similar analysis of patients without natural immunity showed in Vx-001 arm a not statistically significant increase in OS (8.6 months vs 13.2 months, p = 0.27) suggesting that Vx-001 might be efficient in patients with non-immunogenic tumors. Since tumor immunogenicity is known to be associated to patients smoking status, a further analysis was focused according smoking habits. Very interestingly never smokers patients without natural immunity had a much longer OS when their were treated with Vx-001 as compared to placebo (8.6 vs 16.2 months HR = 0.20, p = 0.0008). This effects remained strong if we focused never smokers and former smokers who smoked for a short periode (less than 25 years). In this population OS in the Vx-001 arm was 20.7 months while in the placebo arm was 7.9 months (HR = 0.29, p = 0.0007). Conclusions: These results suggest that Vx-001 might be efficient in patients without natural immunity and particularly in never smokers. Clinical trial identification: NCT01935154, 26/08/2013 Legal entity responsible for the study: Vaxon Biotech Funding: Vaxon Biotech Disclosure: C. Gridelli: Honoraria as advisory board member for Vaxon Biotech. S. Viteri: Consulting (Boehringer Ingelheim, Clovis Oncology, Idea Pharma, Novartis, Promega Biotech Ibérica, Roche, Targovax). Research funding (AbbVie, Ariad, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Clovis Oncology, CytRx, Daiichi Sankyo, GSK, Hanmi, Incyte, Merck KGaA, Novartis, Pfizer, Puma, Roche, Servier, Vaxon). C. Manegold: Travel support from Vaxon. D. Khayat: Consultant or advisory relationship to disclosure: Genomic Health France, Atlantic Sante, Celtic Biotech, Tolabo Radiochir. Stock or other ownership interest: Agenus Inc. J-Y. Douillard: Honoraria as advisory board member for Vaxon Biothec. All other authors have declared no conflicts of interest.