Final outcomes analysis of the cell product SQZ‐PBMC‐HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration

Abstract Cancer vaccines strive to induce robust, antigen‐targeted, T‐cell‐mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ‐PBMC‐HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA‐A*02+ patients. The SQZ‐PBMC‐HPV‐101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ‐PBMC‐HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre‐dose and post‐dose 4 weeks after treatment start. Biomarkers including CD8, MHC‐I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre‐ and post‐dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ‐PBMC‐HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.