A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC
Introduction: Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronch...
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2025-08-01
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| author | Jun-Chieh J. Tsay, MD, MS Antonio Velez, MD Destiny Collazo, BS Isaac Laniado, MD Jamie Bessich, MD Vivek Murthy, MD Andrew DeMaio, MD Samaan Rafeq, MD Benjamin Kwok, MD Fares Darawshy, MD Ray Pillai, MD Kendrew Wong, MD Yonghua Li, MD, PhD Rosemary Schluger, RN Alena Lukovnikova, BS Sofia Roldan, BS Matt Blaisdell, BS Fernanda Paz Kelsey Krolikowski, BS Katherine Gershner, MD Yong Liu, PhD Judy Gong, BA Sara Borghi, PhD Fang Zhou, MD Aristotelis Tsirigos, PhD Harvey Pass, MD Leopoldo N. Segal, MD, MS Daniel H. Sterman, MD |
| author_facet | Jun-Chieh J. Tsay, MD, MS Antonio Velez, MD Destiny Collazo, BS Isaac Laniado, MD Jamie Bessich, MD Vivek Murthy, MD Andrew DeMaio, MD Samaan Rafeq, MD Benjamin Kwok, MD Fares Darawshy, MD Ray Pillai, MD Kendrew Wong, MD Yonghua Li, MD, PhD Rosemary Schluger, RN Alena Lukovnikova, BS Sofia Roldan, BS Matt Blaisdell, BS Fernanda Paz Kelsey Krolikowski, BS Katherine Gershner, MD Yong Liu, PhD Judy Gong, BA Sara Borghi, PhD Fang Zhou, MD Aristotelis Tsirigos, PhD Harvey Pass, MD Leopoldo N. Segal, MD, MS Daniel H. Sterman, MD |
| author_sort | Jun-Chieh J. Tsay, MD, MS |
| collection | DOAJ |
| description | Introduction: Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses. Methods: Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile. Results: Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines—GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2—and effector memory T cells post-BCI. Conclusion: BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment. |
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| language | English |
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| spelling | doaj-art-46e32b042b9441bfae534d7732b8e14c2025-06-28T05:31:14ZengElsevierJTO Clinical and Research Reports2666-36432025-08-0168100849A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLCJun-Chieh J. Tsay, MD, MS0Antonio Velez, MD1Destiny Collazo, BS2Isaac Laniado, MD3Jamie Bessich, MD4Vivek Murthy, MD5Andrew DeMaio, MD6Samaan Rafeq, MD7Benjamin Kwok, MD8Fares Darawshy, MD9Ray Pillai, MD10Kendrew Wong, MD11Yonghua Li, MD, PhD12Rosemary Schluger, RN13Alena Lukovnikova, BS14Sofia Roldan, BS15Matt Blaisdell, BS16Fernanda Paz17Kelsey Krolikowski, BS18Katherine Gershner, MD19Yong Liu, PhD20Judy Gong, BA21Sara Borghi, PhD22Fang Zhou, MD23Aristotelis Tsirigos, PhD24Harvey Pass, MD25Leopoldo N. Segal, MD, MS26Daniel H. Sterman, MD27Division of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New YorkSection of Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North CarolinaImmune Monitoring Laboratory, New York University Grossman School of Medicine, New York, New YorkImmune Monitoring Laboratory, New York University Grossman School of Medicine, New York, New YorkImmune Monitoring Laboratory, New York University Grossman School of Medicine, New York, New YorkDepartment of Pathology, New York University Grossman School of Medicine, New York, New YorkApplied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, New York; Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, New YorkDepartment of Cardiothoracic Surgery, New York University Grossman School of Medicine, New York, New York; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, New YorkDivision of Pulmonary, Critical Care Medicine, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, New York; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NYU Langone Health, New York, New York; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, New York; Corresponding author. Address for correspondence: Daniel H. Sterman, MD, New York University Grossman School of Medicine, 461 1st Avenue, A605, New York, New York 10016.Introduction: Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses. Methods: Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile. Results: Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines—GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2—and effector memory T cells post-BCI. Conclusion: BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.http://www.sciencedirect.com/science/article/pii/S2666364325000669Bronchoscopic cryoimmunotherapyImmunotherapyTumor microenvironmentNSCLCPhase I trial |
| spellingShingle | Jun-Chieh J. Tsay, MD, MS Antonio Velez, MD Destiny Collazo, BS Isaac Laniado, MD Jamie Bessich, MD Vivek Murthy, MD Andrew DeMaio, MD Samaan Rafeq, MD Benjamin Kwok, MD Fares Darawshy, MD Ray Pillai, MD Kendrew Wong, MD Yonghua Li, MD, PhD Rosemary Schluger, RN Alena Lukovnikova, BS Sofia Roldan, BS Matt Blaisdell, BS Fernanda Paz Kelsey Krolikowski, BS Katherine Gershner, MD Yong Liu, PhD Judy Gong, BA Sara Borghi, PhD Fang Zhou, MD Aristotelis Tsirigos, PhD Harvey Pass, MD Leopoldo N. Segal, MD, MS Daniel H. Sterman, MD A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC JTO Clinical and Research Reports Bronchoscopic cryoimmunotherapy Immunotherapy Tumor microenvironment NSCLC Phase I trial |
| title | A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC |
| title_full | A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC |
| title_fullStr | A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC |
| title_full_unstemmed | A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC |
| title_short | A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC |
| title_sort | phase i dose escalation clinical trial of bronchoscopic cryoimmunotherapy in advanced stage nsclc |
| topic | Bronchoscopic cryoimmunotherapy Immunotherapy Tumor microenvironment NSCLC Phase I trial |
| url | http://www.sciencedirect.com/science/article/pii/S2666364325000669 |
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