Telomerase Peptide Vaccination in NSCLC: A Phase II Trial in Stage III Patients Vaccinated after Chemoradiotherapy and an 8-Year Update on a Phase I/II Trial

作者：Paal Fr Brunsvig, Jon Amund Kyte, Christian Kersten, Stein Harald Sundstrøm, Mona Møller, Marta Nyakas, Gaute L. Hansen, Gustav Gaudernack, Steinar Aamdal · 发表于：Clinical Cancer Research · 年份：2011 · DOI：10.1158/1078-0432.ccr-11-1385 · 被引用次数：157 · 研究领域：Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches、Cancer Immunotherapy and Biomarkers

PURPOSE: We report two clinical trials in non-small cell lung 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 chemoradiotherapy and an 8-year update on a previously reported phase I/II trial (CTN-2000). EXPERIMENTAL DESIGN: CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy × 30) and weekly docetaxel (20 mg/m(2)), 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 immunomonitoring showed persisting responses in 13 subjects. Serious adverse events were not observed. Immune responders recorded a median PFS of 371 days, compared with 182 days for nonresponders (P = 0.20). CTN-2000 trial update: 13/24 evaluable subjects developed a GV1001 response. The immune responders achieved increased survival compared with nonresponders (median 19 months vs. 3.5 months; P < 0.001). Follow-up of four long-time survivors showed that they all harbored durable GV1001-specific T-cell memory responses and IFNγ(high)/IL-10(low)/IL-4(low) cytokine profiles. Two patients are free of disease after 108 and 93 months, respectively. CONCLUSIONS: Vaccination with GV1001 is well tolerated, im...