%0 Clinical Trial, Phase I
%T 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.
%A Jimeno A
%A Baranda J
%A Iams WT
%A Park JC
%A Mita M
%A Gordon MS
%A Taylor M
%A Dhani N
%A Leal AD
%A Neupane P
%A Eng C
%A Yeku O
%A Mita A
%A Moser JC
%A Butler M
%A Loughhead SM
%A Jennings J
%A Miselis NR
%A Ji RR
%A Nair N
%A Kornacker M
%A Zwirtes RF
%A Bernstein H
%A Sharei A
%J Invest New Drugs
%V 41
%N 2
%D 04 2023 3
%M 36867316
%F 3.651
%R 10.1007/s10637-023-01342-x
%X 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.