The first cold atmospheric plasma phase I clinical trial for the treatment of advanced solid tumors: A novel 4th treatment arm for cancer.

person Jerome Canady Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD info_outline Jerome Canady, Xiaoqian Cheng, Taisen Zhuang, Saravana Murthy, Aviram Nissan, Steven Gitelis, Lawan Ly, Olivia Jones, Mohammad Adele, Alan T. Blank, Cristina O'Donoghue, Kerstin Stenson, Karen O'Hara, Michael Keidar, Giacomo Basadonna

Authors person Jerome Canady Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD info_outline Jerome Canady, Xiaoqian Cheng, Taisen Zhuang, Saravana Murthy, Aviram Nissan, Steven Gitelis, Lawan Ly, Olivia Jones, Mohammad Adele, Alan T. Blank, Cristina O'Donoghue, Kerstin Stenson, Karen O'Hara, Michael Keidar, Giacomo Basadonna Organizations Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD, Department of General and Oncological Surgery, Sheba Medical Center, Ramat Gan, Israel, Rush University Medical Center, Chicago, IL, Sheba Medical Center, Ramat Gan, Israel, The George Washington University, Washington, DC, DC, University of Massachusetts School of Medicine, Worcester, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company US Medical Innovations Background: Local recurrence contributes to the poor prognosis for patients with Stage IV metastatic or recurrent solid tumors, despite advances in standard care. We report the clinical outcome of intra-operative Cold Atmospheric Plasma (CAP) combined with standard surgical procedures. Methods: The trial was a Phase I, multi-center, open-label, prospective, controlled study. Eligible patients undergoing surgery for advanced Stage IV metastatic or recurrent solid tumors were enrolled and preoperative treatments (neoadjuvant chemotherapy, immunotherapy, radiation, and primary surgery) were permitted. Participants were recruited from Rush University Medical Center in Chicago, Illinois and Sheba Medical Center in Tel HaShomer, Israel. Twenty patients (age 26-85 years) between March 2020 to April 2021 received intra-operative CAP treatment following surgical macroscopic tumor removal. The primary endpoint was safety, and the secondary endpoint was ablation of the local microscopic tumor bed without damaging the surrounding normal tissue. Results: Physiological data (blood pressure, pulse, body temperature, End Tidal CO 2 , and oxygen saturation) was recorded continuously throughout surgery. There were no significant changes (p > 0.05) during intra-operative CAP treatment. One adverse event grade 3 or higher was reported but no adverse events were related to CAP. As of February 13, 2023, 10 patients died of their disease between 3-32 months. Kaplan-Meier overall survival curves show the interim 31-month rate is 24% (95% confidence interval [CI], 5.0 – 100.0%). Median survival is 23 months. For R0 patients, the Kaplan Meier local non-recurrence probability showed that the interim 28-month rate is 75% (n=8; 95% CI, 50.3 – 100.0%) as of February 13, 2023. Histological staining, TUNEL assay, and confocal imaging of the surgical margins revealed cancer cell death and no damage to the surrounding normal tissue. Primary culture of the tumor confirmed total cessation of cancer cell survival. Conclusions: CAP treatment in combination with surgery for high-risk stage IV solid tumors is safe and induces cancer cell death at the surgical bed without damaging non-cancerous tissue. The survival rate in R0-resected CAP-treated patients was significantly improved compared to R1 and R2 patients and local non-recurrence rate for R0 patients was noteworthy. Clinical trial information: NCT04267575. OS analysis for CAP-treated patients (n=20). P=0.0058. Time (Months) Number at Risk Deaths Survival Rate Standard Error Lower 95% CI Upper 95% CI 0 20 0 100% 0.00 1.00 1.00 5 18 2 90% 0.07 0.78 1.00 10 16 3 75% 0.10 0.58 0.97 15 15 0 75% 0.10 0.58 0.97 20 15 1 70% 0.10 0.53 0.93 25 8 0 70% 0.10 0.53 0.93 30 3 2 48% 0.15 0.26 0.88 31 2 1 24% 0.19 0.05 1.00

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