Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer: final results of a randomised phase 2 clinical trial

Cesare Gridelli, Tudor Ciuleanu, Manuel Domine, Aleksandra Szczesna, Isabel Bover, Manuel Cobo, Nikolaos Kentepozidis, Konstantinos Zarogoulidis, Charalabos Kalofonos, Andrzej Kazarnowisz, Magdalena Korozan, Ramon de Las Penas, Margarita Majem, Antonio Chella, Frank Griesinger, Evangelos Bournakis, Parvis Sadjadian, Athanasios Kotsakis, Thierry Chinet, Kostantinos N Syrigos, Pierpaolo Correale, Catherine Gallou, Jeanne- Menez Jamet, Eleni- Kyriaki Vetsika, Kostas Kosmatopoulos, Vassilis Georgoulias, Vx-001-201 trial team, Cesare Gridelli, Tudor Ciuleanu, Manuel Domine, Aleksandra Szczesna, Isabel Bover, Manuel Cobo, Nikolaos Kentepozidis, Konstantinos Zarogoulidis, Charalabos Kalofonos, Andrzej Kazarnowisz, Magdalena Korozan, Ramon de Las Penas, Margarita Majem, Antonio Chella, Frank Griesinger, Evangelos Bournakis, Parvis Sadjadian, Athanasios Kotsakis, Thierry Chinet, Kostantinos N Syrigos, Pierpaolo Correale, Catherine Gallou, Jeanne- Menez Jamet, Eleni- Kyriaki Vetsika, Kostas Kosmatopoulos, Vassilis Georgoulias, Vx-001-201 trial team

Abstract

Background: The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT572 CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC).

Methods: A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS.

Results: Two hundred and twenty-one patients were randomised and 190 (101 and 89 patients in the placebo and the Vx-001 arm, respectively) were analysed for efficacy. There was not treatment-related toxicity >grade 2. The study did not meet its primary endpoint (median OS 11.3 and 14.3 months for the placebo and the Vx-001, respectively; p = 0.86) whereas the median Time to Treatment Failure (TTF) was 3.5 and 3.6 months, respectively. Disease control for >6months was observed in 30 (33.7%) and 26 (25.7%) patients treated with Vx-001 and placebo, respectively. There was no documented objective CR or PR. Long lasting TERT-specific immune response was observed in 29.2% of vaccinated patients who experienced a significantly longer OS compared to non-responders (21.3 and 13.4 months, respectively; p = 0.004).

Conclusion: Vx-001 could induce specific CD8+ immune response but failed to meet its primary endpoint. Subsequent studies have to be focused on the identification and treatment of subgroups of patients able to mount an effective immunological response to Vx-001.

Clinical trial registration: NCT01935154.

Conflict of interest statement

C.G. has received personal fees from MSD, BMS, Astra Zeneca, Roche, Vaxon for advisory board meeting or talk at conferences during the conduct of the study. M.D. has received personal fees from Abbvie, Astra-Zeneca, BMS, Boehringer Ingelheim, Celgene, MSD, Pfizer, Roche, outside of the submitted work. M.M. has received personal fees from Roche, BMS, MSD, Astra Zeneca, Boehringer ingelheim, Lilly, Tesaro, Pfizer for travel grants outside of the submitted work. A.K. has received personal fees from Roche, BMS, MSD, Astra Zeneca, IPSEN, Amgen outside of the submitted work. V.G. reports personal fees from Sanofi for travel grants, outside the submitted work. K.K. and M.J. are shareholder and employee of Vaxon Biotech. C.G. is employee of Vaxon Biotech.

Figures

Fig. 1. OS and TTF in the…
Fig. 1. OS and TTF in the Full Analysis Set (FAS) population.
Comparison of OS a and TTF b between placebo-treated (black line) and Vx-001 treated (blue line) patients.
Fig. 2. Correlation between Vx-001-induced immune response…
Fig. 2. Correlation between Vx-001-induced immune response and clinical response.
OS a and TTF b in Vx-001 immune responders (blue line) and non-responders (black line).

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