Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

PURPOSE: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. METHODS: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. RESULTS: As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). CONCLUSION: Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.

Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

[Kinetics and influencing factors of dimethyl phthalate degradation in aqueous solution by ozonation].

The rate constants for the reaction of higher concentrations of DMP with ozone and hydroxyl radical (*OH) were determined by competition kinetics method, in which nitrobenzene (NB) was selected as the reference organic compound. The effects of *OH inhibitor tert-butyl alcohol, pH and a variety of ions on the degradation of DMP were discussed. Experimental results showed that the degradation of DMP by ozonation followed pseudo-first-order kinetics. The rate constants of DMP with ozone and *OH were (0.064 +/- 0.014) L x (mol x s)(-1) and 3.59 x 10(9) L x (mol x s)(-1), respectively. The system pH decreased due to the carboxylic acids intermediates generated by ozonation at initial pH of 6.08 and 9.07, but the system pH was stabilized in strong alkali or acidic solution. A large number of intermediates resulted in the removal rate of COD lagging behind the degradation efficiency of DMP, and part of the intermediates were difficult to be mineralized. The reaction of DMP with *OH was not inhibited by lower concentrations of tert-butyl alcohol. But the reaction was inhibited when the concentration of tert-butyl alcohol was 90.21 times as high as that of DMP, and the degradation efficiency of DMP decreased from 98.7% to 8.8%. The degradation efficiency of DMP was higher with phosphate buffer solution for pH adjustment than NaOH/H2SO4 solution. Low concentrations of cations and anions had no effects on the degradation efficiency of DMP. High concentrations of SO4(2-), NO3(-) and HPO4(2-) had no remarkable effects on ozonation. But high concentrations of Cl(-) and HCO3(-) inhibited the degradation and the inhibitory effect of HCO3(-) was stronger than Cl(-). The degradation efficiency of DMP was only 50.5% and 26.2%, respectively, after 40 min under 7 097 mg x L(-1) of Cl(-) and 6 093 mg x L(-1) of HCO3(-).