In a phase 1 trial, NSCLC tumors were excised and, while patients received Nivolumab, TILs were expanded ex vivo in the presence of autologous tumor and IL-2. Upon disease progression, patients underwent lymphodepletion followed by TIL and IL-2 infusion; Nivolumab continued. Two of 13 evaluable patients had a complete response, and reduced tumor burden was observed in the remaining 11 patients. T cell reactivity against autologous tumor mutated and TAA peptides was detected in 9 of 20 TIL cultures, and tumor-reactive T cells were detected in peripheral blood months post infusion. T cell polyfunctionality was increased post TIL infusion.
Contributed by Margot O’Toole
ABSTRACT: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ²17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.
Author Info: (1) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. ben.creelan@moffitt.org. (2) Department of Thoracic Oncology, H. Lee Moffitt
Author Info: (1) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. ben.creelan@moffitt.org. (2) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (3) Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (4) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (5) Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (6) Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (7) Cell Therapy Facility, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (8) Department of Sarcoma, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (9) Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (10) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (11) Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (12) Immune and Cellular Therapy Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (13) Immune and Cellular Therapy Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (14) Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (15) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (16) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (17) Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA. (18) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (19) Chemical Biology & Molecular Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (20) Chemical Biology & Molecular Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (21) Chemical Biology & Molecular Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (22) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (23) Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (24) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (25) Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. (26) Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
