Expansion of peripheral T cell clonotypes predict response in patients with small cell neuroendocrine bladder and prostate cancers treated with chemo-immunotherapy in a phase I clinical trial

To explore the impact of immunotherapy, we report a single institution, dual cohort phase Ib study (NCT 03582475) of platinum-based chemotherapy in combination with PD-1 antagonist pembrolizumab to evaluate safety and preliminary efficacy in patients with small cell bladder and small cell/neuroendocrine prostate cancers. To assess the immunologic basis for responses, single cell gene expression and T cell receptor (TCR) sequencing of serial peripheral blood samples revealed a diverse T cell repertoire with expansion of large clonotypes correlating with response.