The influence of inorganic filler particle size and content on tensile strength of polymer composites was discussed in this paper. Based on an interfacial model between inclusion and matrix and the work by Turcsanyi et al., an expression of interfacial adhesion parameter B was proposed, and a new tensile strength equation considering particle diameter effect for polymer composites was derived. A polypropylene (PP) filled with diatomite was fabricated by means of a twin-screw extruder, and the tensile mechanical properties were measured at room temperature to identify the effects of the filler diameter and content on the tensile mechanical properties of these composites. It was found that the tensile strength of these composite systems decreased slightly with an increase of the filler diameter. This equation was initially verified by using these measured data of tensile strength of the PP/diatomite composites. The results show that the predictions were close to the measured data of tensile strength, and the maximum relative errors between them were within 10%.
MET-driven tumors. We investigated the activity of tepotinib in preclinical models and patients with baseline BM in the Phase II VISION study. Methods: Brain penetration was assessed in Wistar rats (n¼3) at tepotinib dose 3.66 mg/kg/h intravenously by determining unbound brain (f u br ) and plasma (f u pl ) concentrations using liquid chromatography with tandem mass spectrometry. Preclinical efficacy was assessed in two patient-derived xenografts (PDX) obtained from BM harboring high MET amplification (MET copy number gain: 11 for LU5349 and 24 for LU5406). NOD-SCID mice with PDX orthotopically implanted into the brain (n¼10/group) were treated with tepotinib 125 mg/kg or vehicle control orally once daily. Intracranial tumor growth was monitored by gadolinium-based MRI. Patients enrolled in VISION Cohort A with METex14 skipping NSCLC and asymptomatic BM (prior brain-specific therapy allowed) received tepotinib 500 mg once daily. Endpoints included systemic response per RECIST v1.1, duration of response (DOR), and progression-free survival (PFS) by independent review committee (IRC). Results: The fraction of unbound tepotinib in rat brain tissue (f u br ¼ 0.4%) was low compared with plasma (f u pl ¼ 4%), indicating high binding in the brain. Upon treatment with tepotinib, both PDX tumors from MET-driven NSCLC BM regressed significantly in orthotopic brain models (mean tumor volume reduction of 63% for LU5406 and 84% for LU5349). VISION Cohort A enrolled 22 patients with baseline BM (identified by IRC or investigator assessment), whose demographic characteristics were similar to the overall population (N¼152). As of July 1, 2020, 21 patients with baseline BM had 9 months' follow-up and were included in efficacy analyses. Confirmed systemic best overall response was partial response in 11 patients for an ORR (95% confidence interval [CI]) of 52.4% (29.8, 74.3), which was comparable to that in overall population (table ). Median DOR (95% CI) was 9.5 months (5.5, not estimable), and median PFS (95% CI) was 9.5 months (5.7, 11.2). Case studies illustrating response of brain lesions in VISION patients will also be presented.
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