Personalized Neoantigen Vaccines and immunotherapy for Urothelial Cancer - Expert Commentary
The primary endpoints were feasibility and safety. A vaccine was successfully prepared (median 20.3 weeks) for 10 of 12 enrolled participants, with a median of 103 neoantigens identified per patient. All participants initiating treatment completed the priming cycle. Treatment-related adverse events were predominantly grade 1, including injection site reactions (40%), fatigue (40%), and fever/chills/rigors (50%). One patient experienced immune-related hepatitis, which resolved with corticosteroids. At a median follow-up of 39 months, three of four patients treated in the adjuvant setting remained free of recurrence. In the metastatic setting, two of five patients with measurable disease achieved objective responses (40%, 95% CI: 5.3–85.3%), including one with complete radiographic resolution of liver metastases. The median progression-free survival and overall survival in the metastatic cohort were 3.5 months (95% CI: 1.5 months–not reached) and 19.1 months (95% CI: 14.1 months–not reached), respectively.
All evaluable participants demonstrated on-treatment emergence of neoantigen-specific T cell responses, with 55% (95% CI: 44.1–65.9%) of selected peptides eliciting responses. These responsive peptides induced a median 10.5-fold increase in IFNγ production from baseline. Both CD8+ and CD4+ T cell responses were observed in all evaluable patients. Notably, patients with no evidence of disease at follow-up demonstrated the largest increases in neoantigen-specific T cell activity.
This important phase I trial demonstrated that combining personalized neoantigen vaccination with atezolizumab was feasible and safe in UC patients, successfully meeting its endpoints. The treatment induced robust neoantigen-specific T cell immunity and showed promising clinical outcomes, warranting further investigation in larger clinical trials.
Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY
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