KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors

Background: No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C. Methods: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was safety. Key secondary end points were pharmacokinetics and objective response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Results: A total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma. Conclusions: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.)

Natural antibacterial agents from arid-region pretreated lignocellulosic biomasses and extracts for the control of lactic acid bacteria in yeast fermentation

Bacterial contamination is one of the major challenges faced by yeast fermentation industries as the contaminating microorganisms produce lactic acid and acetic acid, which reduces the viability of yeast, and hence fermentation yields. The primary bacterial contaminants of yeast fermentations are lactic acid bacteria (LAB). This study aims to identify potential natural antibacterial fractions from raw and pretreated lignocellulosic biomasses found in Abu Dhabi, UAE, in terms of LAB inhibition capacity, allowing growth of the yeast. The analysis was carried out using plating technique. Pretreatment liquid of the mangrove stem Avicennia marina hydrothermally pretreated at 210 °C exhibited the widest inhibition zone with an average diameter of 14.5 mm, followed by the pretreatment liquid of mangrove leaf pretreated at 190 °C, Salicornia bigelovii pretreated at 202 °C and rachis of date palm Phoenix dactylifera pretreated at 200 °C. The compounds responsible for the antibacterial activity will be characterized in further study