Telomerase Peptide Vaccination in NSCLC: A Phase II Trial in Stage III Patients Vaccinated after Chemo-radiotherapy and an 8-years Update on a Phase I/II Trial
Cet article présente les résultats d'un essai de phase II, mené sur 23 patients, et d'un essai de phase I/II, mené sur 26 patients, évaluant des vaccins à base de peptides de la télomérase en complément d'une chimio-radiothérapie pour le traitement d'un cancer du poumon non à petites cellules
Purpose We report two clinical trials in non-small cell cancer (NSCLC) patients evaluating immune response, toxicity and clinical outcome after vaccination with the telomerase peptide GV1001: A phase II trial (CTN-2006) in patients vaccinated after chemo-radiotherapy and an 8-years update on a previously reported phase I/II trial (CTN-2000). Experimental design CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy x 30) and weekly docetaxel (20mg/m2), followed by GV1001 vaccination. CTN-2000: 26 patients were vaccinated with two telomerase peptides (GV1001 and I540). The immune responses were evaluated by T cell proliferation and cytokine assays. Results CTN-2006 trial: A GV1001-specific immune response developed in 16/20 evaluable patients. Long term immuno-monitoring demonstrated persisting responses in 13 subjects. Serious adverse events were not observed. Immune responders recorded a median PFS of 371 days, compared to 182 days for non-responders (p=0.20). CTN-2000 trial update: 13/24 evaluable subjects developed a GV1001 response. The immune responders achieved increased survival compared to non-responders (median 19 months versus 3.5 months; p<0.001). Follow-up of 4 long time survivors demonstrated that they all harboured durable GV1001-specific T cell memory responses and IFNγhigh/IL-10low/IL-4low cytokine profiles. Two patients are free of disease after 108 and 93 months, respectively. Conclusions Vaccination with GV1001 is well tolerated, immunizes the majority of NSCLC patients and establishes durable T cell memory. The considerable immune response rate and low toxicity in the phase II trial support the concept of combining chemo-radiotherapy with vaccination. The survival advantage observed for immune responders warrants a randomized trial.