Search

3110 Background: IBI351(GFH925) is an irreversibly covalent inhibitor of KRASG12C. In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of IBI351 (GFH925) in patients (pts) with advanced solid tumors harboring the KRAS p.G12C mutation. Methods: Pts with locally advanced, recurrent or metastatic solid tumors with KRASG12C mutation for whom standard therapy had failed were enrolled. Phase I dose escalation had an accelerated titration design for dose level 250mg QD and a BOIN design with 450/700/900mg QD. The primary end points were safety and tolerabilityThe secondary end points were pharmacokinetics (PK) and anti-tumor activity of IBI351(GFH925) monotherapy per RECIST v1.1. Results: As of Feb 07 2022, 15 pts (13 men, 2 women; median age: 62 yrs, range: 48–74 yrs) were enrolled, among whom 12 had non-small cell lung cancer (NSCLC), and 3 had colorectal cancer (CRC). 4 pts had ≥3 prior lines of treatment (tx). Median tx duration was 66.5 ds (range: 21–98 ds). No dose-limiting toxicity (DLT) or any ≥grade 3 treatment-related adverse events were observed in any dose cohorts. A total of 12 patients (80.0%) had treatment-related adverse events (grade 1, n = 6; grade 2, n = 6). By investigator-assessment, tumor response was evaluated in 9 pts (4 with ≥2 assessments); 6 pts had not reached their first assessment. 2 pts had PR (1 NSCLC at wks 12, 450mg, tx ongoing; 1 CRC at wks 6, 700mg, tx ongoing), 4 pts (NSCLC) had SD, and 3 pts had PD (1 NSCLC at wks 12, 2 CRC at wks 6). As data cut-off date, 11 pts were continuing to receive IBI351 (GFH925). Conclusions: IBI351(GFH925) was well-tolerated without unanticipated adverse events across all doses explored in pts with advanced solid tumors harboring the KRAS p.G12C mutation. The data also demonstrated the preliminary efficacy signal of IBI351 (GFH925) in previously treated advanced NSCLC and CRC. Clinical trial information: NCT05005234.

The primary clinical diagnosis of Alzheimer’s disease is mainly based on medical history and neuropsychiatric inventory. It is urgent to seek biological indicators with better sensitivity and higher specificity to clinically diagnose and evaluate Alzheimer’s disease. In this work, an electrophoretic method based on 2-thiobarbituric acid derivatization and amperometric detection was developed to determine formaldehyde as a urinary biomarker of Alzheimer’s disease. Under the optimum conditions, the formaldehyde derivative was well separated from the coexisting interferences in urine sample. The limit of detection for formaldehyde was 80.0 nM (2.4 ng/ mL) based on an electrophoretic stacking technology. The average recovery values were in the range of 91.7–110%, and the relative standard deviation values were less than 4.1%. This method has been applied to analyze human urine samples from healthy volunteers and patients with different degrees of Alzheimer’s disease. The assay results showed that the ...

An electrophoretic method was developed for the determination of several important catecholamine markers, namely norepinephrine, epinephrine, dopamine, metanephrine, vanillylmandelic acid and homovanillic acid in urine samples. Under the optimum conditions, the six marker compounds could be well separated with the major coexisting interference compound uric acid within 24 min at a separation voltage of 16 kV in a borate running buffer(80 mmol/L, pH=9.48). Highly linear response can be obtained over three orders of magnitude for the above markers with the low limits of detection ranging from 1.0 ng/mL to 5.0 ng/mL(S/N=3). The proposed capillary electrophoresis with amperometric detection(CE-AD) method has been used to simultaneously determine the six catecholamine markers in urine samples of healthy volunteers and patients suffering from different diseases avoiding redundant measurements and high assay cost; and the electrochemical profiles can suggest more diagnostic information of multiple diseases, which provides a promising and convenient entry into primary diagnoses of several clinical diseases.

An indirect high-performance capillary electrophoresis with amperometric detection (CE-AD) method has been developed for determination of lactic acid (LA) in body fluids of lactating postpartum women. Several important factors such as the running buffer additive and concentration, the working electrode potential, the pH value and concentration of the running buffer, the separation voltage and injection time were investigated. Under the optimum conditions, LA could be well separated with co-existing interferences including uric acid (UA) in real samples in a 90-cm-length capillary at separation voltage of 12 kV in 4.0 × 10−6 g mL−1 3,4-dihydroxybenzylamine (DHBA)/40 mmol L−1 H3BO3–Na2B4O7 buffer (pH 7.8). The linearity between peak current and concentration of LA was over three orders of magnitude with detection limit of 5.00 × 10−7 g mL−1 (S/N = 3). This proposed method has been successfully used to study the effects of moderate exercise on LA content in breast milk and urine samples of lactating postpartum women, and assay results showed that LA content in breast milk can return to normal level through 60 min rest without decreasing acceptance by breast-feeding infants, although the LA level did increase by 4–6 times in both breast milk and urine samples at 10 min after moderate exercise.

A simple and reliable method based on capillary electrophoresis with electrochemical detection (CE–ED) was applied to study the effect of aerobic exercises on creatinine and uric acid concertration in saliva and urine. The pH value, the running buffer concentration, the SDS concentration, separation voltage, injection time and the potential applied to the working electrode were investigated to find the optimum conditions. The detection limits (S/N = 3) for creatinine and uric acid were 3.6 μmol L−1 and 0.86 μmol L−1, respectively. This method was successfully used in the rapid analysis of creatinine and uric acid in saliva samples. After aerobic exercises, creatinine concentration decreased, and uric acid concentration increased in saliva. In urine, the concentrations of creatinine and uric acid both increased after exercise.

Hexanal (Hex) and heptanal (Hep) in human blood have been regarded as potential biomarkers of lung cancer. In this work, a hollow-fiber liquid-phase microextraction (HF-LPME) method has been developed for the preconcentration of these trace aldehydes in urine samples. After derivatization with an electroactive compound 2-thiobarbituric acid, these two non-electroactive aldehydes were converted to electroactive adducts, therefore detectable by capillary zone electrophoresis with amperometric detection (CZE-AD) approach. Experimental conditions of derivatization, extraction, electrophoretic separation and detection were optimized. Under the optimum conditions, the enrichment factors for Hex and Hep could reach 320 and 355, respectively. The limits of detection for Hex and Hep were 2.7 and 0.97 nM, respectively; the average recoveries were in the range of 61–95% and relative standard deviation (RSD) values less than 8.5%. The present method has been applied to quantitative analysis of two biomarkers in human urine in lieu of blood samples, and the assay results showed that the contents of Hex (0.99–6.7 μM) and Hep (2.5–6.4 μM) found in the urine sample of the lung cancer patients were significantly higher than those in the healthy volunteers, liver cancer patients, as well as diabetics. The proposed HF-LPME/CZE-AD method may provide a potential alternative for early non-invasive diagnosis of lung cancer disease.