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Background: MET exon 14 skipping mutations occur in 3-4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation.
Methods: The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2). The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by independent radiology review in cohort 1. The key secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Results: A total of 28 patients (23 in cohort 1 and 5 in cohort 2) were enrolled between March 2018 and February 2020. The primary endpoint was met as the ORR (90% confidence interval: CI) in cohort 1 was 38.1% (20.6-58.3). Median DoR, PFS, and OS (95% CI) were 7.6 (1.9-NE), 5.7 (2.1-11.3), 9.1 (4.0-19.9) months, respectively, in cohort 1. ORR in cohort 2 was 40.0% (18.9-92.4). The safety signals were generally consistent with the known safety profile of crizotinib.
Conclusions: Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations.
Clinical Trial Information: UMIN000031623.
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http://dx.doi.org/10.1007/s10147-024-02543-x | DOI Listing |
Diabetes
September 2025
Institute for Physical Activity and Nutrition, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria, Australia.
Unlabelled: Despite stimulating glucagon secretion, the mechanisms by which protein ingestion lowers glucose excursions remain unclear. We investigated this using the triple stable isotope glucose tracer technique to measure postprandial glucose fluxes. Eleven healthy adults completed three trials, ingesting 25 g glucose (25G; 100 kcal), 50 g glucose (50G; 200 kcal), or 25 g glucose plus 25 g whey protein (25WG; 200 kcal).
View Article and Find Full Text PDFJ Alzheimers Dis
September 2025
Paula Costa-Urrutia Medical Affairs, Terumo BCT, Edificio Think MVD, Montevideo, Uruguay.
BackgroundTherapeutic plasma exchange (TPE) with albumin replacement has emerged as a potential treatment for Alzheimer's disease (AD). The AMBAR trial showed that TPE could slow cognitive and functional decline, along with changes in core and inflammatory biomarkers in cerebrospinal fluid.ObjectiveTo evaluate the safety and effectiveness of TPE in a real-world setting in Argentina.
View Article and Find Full Text PDFJAMA Psychiatry
September 2025
Denovo Biopharma LLC, San Diego, California.
Importance: This study represents a first successful use of a genetic biomarker to select potential responders in a prospective study in psychiatry. Liafensine, a triple reuptake inhibitor, may become a new precision medicine for treatment-resistant depression (TRD), a major unmet medical need.
Objective: To determine whether ANK3-positive patients with TRD benefit from a 1-mg and/or 2-mg daily oral dose of liafensine, compared with placebo, in a clinical trial.
Am J Clin Oncol
September 2025
Servicio de Oncología Médica HM CIOCC, Hospital Universitario HM Sanchinarro, Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela, Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain.
Objectives: To evaluate the association between the KRAS mutational load and the histologic tumor response in patients with resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant treatment (NAC) with pegylated liposomal irinotecan in combination with oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX).
Methods: This was a multicenter, single-arm, interventional, open-label, phase 2 trial in patients 18 years or older who had histologically or cytologically confirmed PDAC and were candidates for surgery and received neoadjuvant NALIRIFOX. The primary outcome was determination of the association between the KRAS mutational load and the histologic tumor response after chemotherapy.
Int J Surg
September 2025
Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University.
Diabetic retinopathy (DR) remains a leading cause of preventable blindness worldwide, with the affected population projected to reach 270 million by 2045. Our study analyzed 2 434 interventional trials registered between 2007 and 2024 in the Informa Pharma Intelligence database and found that anti-VEGF agents dominate the therapeutic landscape-bevacizumab represents 24.0 % of studies, ranibizumab 15.
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