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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.
Jimeno, Antonio; Baranda, Joaquina; Iams, Wade T; Park, Jong Chul; Mita, Monica; Gordon, Michael S; Taylor, Matthew; Dhani, Neesha; Leal, Alexis D; Neupane, Prakash; Eng, Cathy; Yeku, Oladapo; Mita, Alain; Moser, Justin C; Butler, Marcus; Loughhead, Scott M; Jennings, Julia; Miselis, Nathan R; Ji, Rui-Ru; Nair, Nitya; Kornacker, Martin; Zwirtes, Ricardo F; Bernstein, Howard; Sharei, Armon.
Afiliación
  • Jimeno A; University of Colorado Comprehensive Cancer Center, 12801 East 17th Avenue, Room L18-8101B, Aurora, CO, 80045, USA. Antonio.Jimeno@cuanschutz.edu.
  • Baranda J; University of Kansas Cancer Center, Fairway, KS, USA.
  • Iams WT; Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
  • Park JC; Massachusetts General Hospital, Boston, MA, USA.
  • Mita M; Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Gordon MS; Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, AZ, USA.
  • Taylor M; Providence Cancer Institute, Portland, OR, USA.
  • Dhani N; University Health Network Princess Margaret Cancer Centre, Toronto, Canada.
  • Leal AD; University of Colorado Comprehensive Cancer Center, 12801 East 17th Avenue, Room L18-8101B, Aurora, CO, 80045, USA.
  • Neupane P; University of Kansas Cancer Center, Fairway, KS, USA.
  • Eng C; Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
  • Yeku O; Massachusetts General Hospital, Boston, MA, USA.
  • Mita A; Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Moser JC; Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, AZ, USA.
  • Butler M; University Health Network Princess Margaret Cancer Centre, Toronto, Canada.
  • Loughhead SM; SQZ Biotechnologies, Watertown, MA, USA.
  • Jennings J; SQZ Biotechnologies, Watertown, MA, USA.
  • Miselis NR; SQZ Biotechnologies, Watertown, MA, USA.
  • Ji RR; SQZ Biotechnologies, Watertown, MA, USA.
  • Nair N; Hoffmann-La Roche, Basel, Switzerland.
  • Kornacker M; Hoffmann-La Roche, Basel, Switzerland.
  • Zwirtes RF; SQZ Biotechnologies, Watertown, MA, USA.
  • Bernstein H; SQZ Biotechnologies, Watertown, MA, USA.
  • Sharei A; SQZ Biotechnologies, Watertown, MA, USA.
Invest New Drugs ; 41(2): 284-295, 2023 04.
Article en En | MEDLINE | ID: mdl-36867316
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Oncogénicas Virales / Infecciones por Papillomavirus / Neoplasias Límite: Humans Idioma: En Revista: Invest New Drugs Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Oncogénicas Virales / Infecciones por Papillomavirus / Neoplasias Límite: Humans Idioma: En Revista: Invest New Drugs Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos