Introduction
Janus kinase-signal transducer, tumor
TUMOR, SOLID TUMORS
Immune checkpoint receptors are expressed on tumor, stromal, and immune cells, and negatively regulate the immune response in the tumor microenvironment (TME; ref. Excessive Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling within the TME may reduce antitumor responses, suggesting JAK enzymes could be potential therapeutic targets (PI3Kδ is enriched in hematopoietic cells, including lymphocytes and myeloid cells (We conducted a phase Ib platform study to explore the clinical safety and tolerability of increasing doses of either itacitinib or parsaclisib in combination with established dosing of the PD-1 inhibitor pembrolizumab in patients with solid tumors. Paired biomarker analysis of treatments and changes within the TME were also examined to provide insight on incorporating JAK1 or PI3Kδ inhibition.