{Reference Type}: Clinical Trial, Phase I
{Title}: 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.
{Author}: Jimeno A;Baranda J;Iams WT;Park JC;Mita M;Gordon MS;Taylor M;Dhani N;Leal AD;Neupane P;Eng C;Yeku O;Mita A;Moser JC;Butler M;Loughhead SM;Jennings J;Miselis NR;Ji RR;Nair N;Kornacker M;Zwirtes RF;Bernstein H;Sharei A;
{Journal}: Invest New Drugs
{Volume}: 41
{Issue}: 2
{Year}: 04 2023 3
{Factor}: 3.651
{DOI}: 10.1007/s10637-023-01342-x
{Abstract}: 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. 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. Eighteen patients were enrolled at doses ranging from 0.5 × 106 to 5.0 × 106 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. SQZ-PBMC-HPV was well tolerated; 5.0 × 106 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.