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This first-in-human Phase I study assessed the safety and tolerability of the industrial-grade batch of AV-22 dry medicinal extract (Gratiola officinalis L.) (Developing organization: Saratov State Medical University named after V.I. Razumovsky, Ministry of Health of Russia). Objective — To evaluate the safety, tolerability, and maximum tolerated dose (MTD) of a single oral dose of AV 22 in patients with advanced genitourinary cancers. Material and Methods — An open-label, single-center, dose-escalation study was conducted using the classic 3+3 design [12]. Twenty patients with advanced genitourinary cancers were sequentially enrolled in five dose cohorts (125, 250, 375, 500, and 625 mg). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Tumor response was assessed at day 28 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Pharmacokinetic analyses quantified plasma concentrations of verbascoside, cucurbitacin D, cucurbitacin E, and cucurbitacin I after oral administration. Concentrations were quantified using a validated method of high-performance liquid chromatography with a mass-selective detector (HPLC-MS/MS) with a linear range of 1-1000 ng/mL (lower limit of quantification (LLOQ): 1 ng/mL). Serial blood samples for pharmacokinetic analysis were collected before and after drug administration at designated time points: 0.5, 1, 3, 6, 9, 12, 15, 18, 24, and 36 hours, as well as on days 7, 14, and 28 (all samples obtained in the morning after an overnight fast). Results — All 20 patients completed the observation protocol (mean age =65.8±9.6 years). No dose limiting toxicity (DLT) or serious adverse events were reported, and the maximum tolerated dose (MTD) was not reached at any dose level up to 625 mg. Plasma concentrations of all analyzed active components (verbascoside, cucurbitacins D, E, and I) were below the lower limit of quantification (LLOQ=1 ng/mL) at all sampling time points, precluding the calculation of standard pharmacokinetic parameters (e.g., AUC, Cₘₐₓ, Tₘₐₓ, t₁/₂). Statistically significant changes in individual laboratory parameters (e.g., hemoglobin, thrombin time, and total bilirubin) were small in magnitude and were not accompanied by clinically significant deviations. Follow-up computed tomography or magnetic resonance imaging (CT/MRI) was performed in all patients on day 28: all 20 patients (100%) achieved stable disease, with no partial or complete responses or progressive disease. Conclusion — A single 125-625 mg dose of AV-22 exhibited a favorable safety profile and tolerability in patients with advanced genitourinary cancers. The data obtained justify further studies with multiple doses and extended biomarker monitoring.