In a Phase 1 study of 18 HLA-A*02+ patients with advanced/metastatic HPV16+ solid tumors, Jimeno et al. showed good tolerance to every 3 week dosing of 0.5 - 5.0×106 live cells/kg of autologous PBMCs loaded with HPV16 E6/E7 Ags by microfluidic squeezing and then matured by CpG. A median of 4 treatments of the highest dose were given, with no DLTs. Most related TEAEs were Grade 1-2, with one self-limiting Grade 2 CRS. Pharmacodynamic changes were seen in multiple, including CPI-refractory, patients. Tumor biopsies in 3 patients showed CD8+ TIL increases, including a case with increased PD-L1+ cell densities and reduced HPV+ cell numbers and lesion volume.
Contributed by Paula Hochman
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 _ 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. 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.
Author Info: (1) University of Colorado Comprehensive Cancer Center, 12801 East 17th Avenue, Room L18-8101B, Aurora, CO, 80045, USA. Antonio.Jimeno@cuanschutz.edu. (2) University of Kansas Canc
Author Info: (1) University of Colorado Comprehensive Cancer Center, 12801 East 17th Avenue, Room L18-8101B, Aurora, CO, 80045, USA. Antonio.Jimeno@cuanschutz.edu. (2) University of Kansas Cancer Center, Fairway, KS, USA. (3) Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. (4) Massachusetts General Hospital, Boston, MA, USA. (5) Cedars-Sinai Medical Center, Los Angeles, CA, USA. (6) Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, AZ, USA. (7) Providence Cancer Institute, Portland, OR, USA. (8) University Health Network Princess Margaret Cancer Centre, Toronto, Canada. (9) University of Colorado Comprehensive Cancer Center, 12801 East 17th Avenue, Room L18-8101B, Aurora, CO, 80045, USA. (10) University of Kansas Cancer Center, Fairway, KS, USA. (11) Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. (12) Massachusetts General Hospital, Boston, MA, USA. (13) Cedars-Sinai Medical Center, Los Angeles, CA, USA. (14) Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, AZ, USA. (15) University Health Network Princess Margaret Cancer Centre, Toronto, Canada. (16) SQZ Biotechnologies, Watertown, MA, USA. (17) SQZ Biotechnologies, Watertown, MA, USA. (18) SQZ Biotechnologies, Watertown, MA, USA. (19) SQZ Biotechnologies, Watertown, MA, USA. (20) Hoffmann-La Roche, Basel, Switzerland. (21) Hoffmann-La Roche, Basel, Switzerland. (22) SQZ Biotechnologies, Watertown, MA, USA. (23) SQZ Biotechnologies, Watertown, MA, USA. (24) SQZ Biotechnologies, Watertown, MA, USA.
