Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ- PBMC-HPV) in HLA-A*02+ patients with HPV16+ Solid Tumors

Purpose: We conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze® technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02 + patients with advanced/metastatic HPV16 + cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8 + cells, and demonstrated antitumor activity. Methods Administration of SQZ-PBMC-HPV was every 3 weeks. Enrollment followed a modified 3 + 3 design with primary objectives to define safety, tolerability, and the recommended Phase 2 dose. Secondary and exploratory objectives were antitumor activity, manufacturing feasibility, and pharmacodynamic evaluation of immune responses. Results Eighteen patients were enrolled at doses ranging from 0.5 × 10 6 to 5.0 × 10 6 live cells/kg. Manufacture proved feasible and required < 24 h within the overall vein-to-vein time of 1–2 weeks; at the highest dose, a median of 4 doses were administered. No DLTs were observed. Most related TEAEs were Grade 1–2, and one Grade 2 cytokine release syndrome SAE was reported. Tumor biopsies in three patients showed 2 to 8-fold increases in CD8 + tissue infiltrating lymphocytes, including a case that exhibited increased MHC-I + and PD-L1 + cell densities and reduced numbers of HPV + cells. Clinical benefit was documented for the latter case. Conclusions SQZ-PBMC-HPV was well tolerated; 5.0 × 10 6 live cells/kg with double priming was chosen as the recommended Phase 2 dose. Multiple participants exhibited pharmacodynamic changes consistent with immune responses supporting the proposed mechanism of action for SQZ-PBMC-HPV, including patients previously refractory to checkpoint inhibitors.