Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study

Myeong Geun Choi; Gun Woo Son; Mi Young Choi; Jae Seob Jung; Jin Kyung Rho; Wonjun Ji; Byeong Gon Yoon; Jong Min Jo; Yong Man Kim; Dae Hyun Ko; Jae Cheol Lee; Chang Min Choi

doi:10.1136/jitc-2023-008585

Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study

Myeong Geun Choi, Gun Woo Son, Mi Young Choi, Jae Seob Jung, Jin Kyung Rho, Wonjun Ji, Byeong Gon Yoon, Jong Min Jo, Yong Man Kim, Dae Hyun Ko, Jae Cheol Lee, Chang Min Choi

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Background Choosing treatments for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with osimertinib resistance is challenging. We evaluated the safety and efficacy of SNK01 (autologous natural killer (NK) cells) in combination with cytotoxic chemotherapy and/or cetuximab (an anti-EGFR monoclonal antibody) in treating EGFR-mutated NSCLC in this non-clinical and phase I/IIa clinical trial. Methods We developed a cell line-derived xenograft-humanized mouse model with an osimertinib-resistant lung cancer cell line. The mice were divided into four groups based on treatment (no treatment, cetuximab, SNK01, and combination groups) and treated weekly for 5 weeks. In the clinical study, 12 patients with EGFR-mutated NSCLC who failed prior tyrosine kinase inhibitor (TKI) received SNK01 weekly in combination with gemcitabine/carboplatin (n=6) or cetuximab/gemcitabine/carboplatin (n=6) and dose escalation of SNK01 following the “3+3” design. Results In the non-clinical study, an increase in NK cells in the blood and enhanced NK cell tumor infiltration were observed in the SNK01 group. The volume of tumor extracted after treatment was the smallest in the combination group. In the clinical study, 12 patients (median age, 60.9 years; all adenocarcinoma cases) received SNK01 weekly for 7–8 weeks (4×10⁹ cells/dose (n=6); 6×10⁹ cells/dose (n=6)). The maximum feasible dose of SNK01 was 6×10⁹ cells/dose without dose-limiting toxicity. Efficacy outcomes showed an objective response rate of 25%, disease control rate of 100%, and median progression-free survival of 143 days. Conclusion SNK01 in combination with cytotoxic chemotherapy, including cetuximab, for EGFR-mutated NSCLC with TKI resistance was safe and exerted a potential antitumor effect.

Original language	English
Article number	e008585
Journal	Journal for ImmunoTherapy of Cancer
Volume	12
Issue number	3
DOIs	https://doi.org/10.1136/jitc-2023-008585
State	Published - 27 Mar 2024

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© Author(s) (or their employer(s)) 2024.

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Choi, M. G., Son, G. W., Choi, M. Y., Jung, J. S., Rho, J. K., Ji, W., Yoon, B. G., Jo, J. M., Kim, Y. M., Ko, D. H., Lee, J. C., & Choi, C. M. (2024). Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study. Journal for ImmunoTherapy of Cancer, 12(3), Article e008585. https://doi.org/10.1136/jitc-2023-008585

Choi, Myeong Geun ; Son, Gun Woo ; Choi, Mi Young et al. / Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer : non-clinical mouse model and phase I/IIa clinical study. In: Journal for ImmunoTherapy of Cancer. 2024 ; Vol. 12, No. 3.

@article{1267ecaadc1b4080af6dd1aa7c206877,

title = "Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study",

abstract = "Background Choosing treatments for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with osimertinib resistance is challenging. We evaluated the safety and efficacy of SNK01 (autologous natural killer (NK) cells) in combination with cytotoxic chemotherapy and/or cetuximab (an anti-EGFR monoclonal antibody) in treating EGFR-mutated NSCLC in this non-clinical and phase I/IIa clinical trial. Methods We developed a cell line-derived xenograft-humanized mouse model with an osimertinib-resistant lung cancer cell line. The mice were divided into four groups based on treatment (no treatment, cetuximab, SNK01, and combination groups) and treated weekly for 5 weeks. In the clinical study, 12 patients with EGFR-mutated NSCLC who failed prior tyrosine kinase inhibitor (TKI) received SNK01 weekly in combination with gemcitabine/carboplatin (n=6) or cetuximab/gemcitabine/carboplatin (n=6) and dose escalation of SNK01 following the “3+3” design. Results In the non-clinical study, an increase in NK cells in the blood and enhanced NK cell tumor infiltration were observed in the SNK01 group. The volume of tumor extracted after treatment was the smallest in the combination group. In the clinical study, 12 patients (median age, 60.9 years; all adenocarcinoma cases) received SNK01 weekly for 7–8 weeks (4×109 cells/dose (n=6); 6×109 cells/dose (n=6)). The maximum feasible dose of SNK01 was 6×109 cells/dose without dose-limiting toxicity. Efficacy outcomes showed an objective response rate of 25\%, disease control rate of 100\%, and median progression-free survival of 143 days. Conclusion SNK01 in combination with cytotoxic chemotherapy, including cetuximab, for EGFR-mutated NSCLC with TKI resistance was safe and exerted a potential antitumor effect.",

author = "Choi, \{Myeong Geun\} and Son, \{Gun Woo\} and Choi, \{Mi Young\} and Jung, \{Jae Seob\} and Rho, \{Jin Kyung\} and Wonjun Ji and Yoon, \{Byeong Gon\} and Jo, \{Jong Min\} and Kim, \{Yong Man\} and Ko, \{Dae Hyun\} and Lee, \{Jae Cheol\} and Choi, \{Chang Min\}",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2024.",

year = "2024",

month = mar,

day = "27",

doi = "10.1136/jitc-2023-008585",

language = "English",

volume = "12",

journal = "Journal for ImmunoTherapy of Cancer",

issn = "2051-1426",

publisher = "BMJ Publishing Group",

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Choi, MG, Son, GW, Choi, MY, Jung, JS, Rho, JK, Ji, W, Yoon, BG, Jo, JM, Kim, YM, Ko, DH, Lee, JC & Choi, CM 2024, 'Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study', Journal for ImmunoTherapy of Cancer, vol. 12, no. 3, e008585. https://doi.org/10.1136/jitc-2023-008585

Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study. / Choi, Myeong Geun; Son, Gun Woo; Choi, Mi Young et al.
In: Journal for ImmunoTherapy of Cancer, Vol. 12, No. 3, e008585, 27.03.2024.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer

T2 - non-clinical mouse model and phase I/IIa clinical study

AU - Choi, Myeong Geun

AU - Son, Gun Woo

AU - Choi, Mi Young

AU - Jung, Jae Seob

AU - Rho, Jin Kyung

AU - Ji, Wonjun

AU - Yoon, Byeong Gon

AU - Jo, Jong Min

AU - Kim, Yong Man

AU - Ko, Dae Hyun

AU - Lee, Jae Cheol

AU - Choi, Chang Min

PY - 2024/3/27

Y1 - 2024/3/27

N2 - Background Choosing treatments for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with osimertinib resistance is challenging. We evaluated the safety and efficacy of SNK01 (autologous natural killer (NK) cells) in combination with cytotoxic chemotherapy and/or cetuximab (an anti-EGFR monoclonal antibody) in treating EGFR-mutated NSCLC in this non-clinical and phase I/IIa clinical trial. Methods We developed a cell line-derived xenograft-humanized mouse model with an osimertinib-resistant lung cancer cell line. The mice were divided into four groups based on treatment (no treatment, cetuximab, SNK01, and combination groups) and treated weekly for 5 weeks. In the clinical study, 12 patients with EGFR-mutated NSCLC who failed prior tyrosine kinase inhibitor (TKI) received SNK01 weekly in combination with gemcitabine/carboplatin (n=6) or cetuximab/gemcitabine/carboplatin (n=6) and dose escalation of SNK01 following the “3+3” design. Results In the non-clinical study, an increase in NK cells in the blood and enhanced NK cell tumor infiltration were observed in the SNK01 group. The volume of tumor extracted after treatment was the smallest in the combination group. In the clinical study, 12 patients (median age, 60.9 years; all adenocarcinoma cases) received SNK01 weekly for 7–8 weeks (4×109 cells/dose (n=6); 6×109 cells/dose (n=6)). The maximum feasible dose of SNK01 was 6×109 cells/dose without dose-limiting toxicity. Efficacy outcomes showed an objective response rate of 25%, disease control rate of 100%, and median progression-free survival of 143 days. Conclusion SNK01 in combination with cytotoxic chemotherapy, including cetuximab, for EGFR-mutated NSCLC with TKI resistance was safe and exerted a potential antitumor effect.

AB - Background Choosing treatments for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with osimertinib resistance is challenging. We evaluated the safety and efficacy of SNK01 (autologous natural killer (NK) cells) in combination with cytotoxic chemotherapy and/or cetuximab (an anti-EGFR monoclonal antibody) in treating EGFR-mutated NSCLC in this non-clinical and phase I/IIa clinical trial. Methods We developed a cell line-derived xenograft-humanized mouse model with an osimertinib-resistant lung cancer cell line. The mice were divided into four groups based on treatment (no treatment, cetuximab, SNK01, and combination groups) and treated weekly for 5 weeks. In the clinical study, 12 patients with EGFR-mutated NSCLC who failed prior tyrosine kinase inhibitor (TKI) received SNK01 weekly in combination with gemcitabine/carboplatin (n=6) or cetuximab/gemcitabine/carboplatin (n=6) and dose escalation of SNK01 following the “3+3” design. Results In the non-clinical study, an increase in NK cells in the blood and enhanced NK cell tumor infiltration were observed in the SNK01 group. The volume of tumor extracted after treatment was the smallest in the combination group. In the clinical study, 12 patients (median age, 60.9 years; all adenocarcinoma cases) received SNK01 weekly for 7–8 weeks (4×109 cells/dose (n=6); 6×109 cells/dose (n=6)). The maximum feasible dose of SNK01 was 6×109 cells/dose without dose-limiting toxicity. Efficacy outcomes showed an objective response rate of 25%, disease control rate of 100%, and median progression-free survival of 143 days. Conclusion SNK01 in combination with cytotoxic chemotherapy, including cetuximab, for EGFR-mutated NSCLC with TKI resistance was safe and exerted a potential antitumor effect.

UR - https://www.scopus.com/pages/publications/85189257405

U2 - 10.1136/jitc-2023-008585

DO - 10.1136/jitc-2023-008585

M3 - Article

C2 - 38538093

AN - SCOPUS:85189257405

SN - 2051-1426

VL - 12

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

IS - 3

M1 - e008585

ER -

Choi MG, Son GW, Choi MY, Jung JS, Rho JK, Ji W et al. Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study. Journal for ImmunoTherapy of Cancer. 2024 Mar 27;12(3):e008585. doi: 10.1136/jitc-2023-008585