Background Tumor ablation is a minimally invasive technique commonly used to treat solid tumors in the liver, kidney, bone and lung and is based on thermal and nonthermal approaches. Local and in-situ tumor ablation methods demonstrated enhance anti-tumor immune responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. Nitric oxide (NO) is a colorless gas and is short-lived free radical. It is ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes, as well as in numerous pathological conditions. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated its anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor bearing mice with ultra-high concentrations of nitric oxide (UNO) upregulates innate and adaptive immune cells both locally and systemically. Beyond Air and Beyond Cancer is currently conducting a first-in-human, first-in-class Phase 1 safety and preliminary efficacy clinical study of UNO at multiple institutions in Israel.
Methods The study is a 2-part Phase 1 trial with a Dose Escalation and a Dose Expansion portion (NCT05351502). A conventional 3+3 dose escalation will evaluate three single escalating doses of UNO: 25,000, 50,000, and 100,000 ppm delivered intratumorally over 5 minutes at a flow rate of 0.2 liters-per-minute in subjects with relapsed or refractory unresectable primary or metastatic cutaneous and subcutaneous solid tumors. Upon determination of the maximum tolerated dose or biological effective dose, the recommended Phase 2 dose will be further evaluated in the Dose Expansion potion of the study. RECIST version 1.1 will be utilized to assess the rate of malignant tumor response after UNO administration and toxicity will be graded per NCI CTCAE version 5.0. Up to thirty-eight enrolled subjects are anticipated. This study was approved by the Israel Ministry of Health (Form 8; 202124820) as well as the participating institution’s Ethics Board. Written informed consent was obtained for all enrolled subjects and a copy of the written consent is available for review.
Trial Registration NCT05351502
Consent Written informed consent was obtained from the patient for publication of this abstract and any accompany images. A copy of the written consent is available for review by the Editor of this journal.
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