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To posture for this potential scenario and to deter further aggression in Europe, USEUCOM is executing a logistics strategy that assures access and freedom of movement, improves logistics infrastructure posture, leverages commercial capacity in Europe and most importantly, improves vertical and horizontal synchronization with the Joint Logistics Enterprise. In line with the National Defense Strategy and critical to this effort, we continue to work with NATO, Supreme Headquarters Allied Powers Europe, partner and host nations, and the European Union (EU) to maximize the entire Theater Distribution Network. To deploy and place one ABCT in Europe, it takes roughly seven different organizations from U.S. Transportation Command (USTRANSCOM) and U.S. Army Europe partnering with host-nation military and local governments to plan, prepare, and execute movement of equipment and personnel into final tactical assembly areas. USEUCOM, NATO, and EU organizations work together to integrate logistics command and control and align infrastructure improvements to provide multi-national solutions for logistics support to steady-state and potential crisis operations.

The Secretaries of State and Defense meet with President Zelenskyy in Kyiv vowing more aid and the return of American diplomats as the U.S. faces questions about its objective to weaken Russia. Russia continues its offensive in eastern Ukraine, and according to Ukrainian officials, and targeting several railway stations in central and western Ukraine as well. Judge Arthur Engoron has found former President Donald Trump in contempt in the civil case over his business dealings. GUESTS: Volodymyr Omelyan

During the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.

Biomarkers and Immune MonitoringO1 Combinatorial CD8+ and PD-L1+ cell densities correlate with response and improved survival in non-small cell lung cancer (NSCLC) patients treated with durvalumabSonja Althammer1, Keith Steele2, Marlon Rebelatto2, Tze Heng Tan1, Tobias Wiestler1, Guenter Schmidt1, Brandon Higgs2, Xia Li2, Li Shi2, Xiaoping Jin2, Joyce Antal2, Ashok Gupta2, Koustubh Ranade2, Gerd Binning11Definiens AG, Munich, Bayern, Germany; 2MedImmune, Gaithersburg, MD, USACorrespondence: Brandon Higgs (higgsb@medimmune.com) Background Immunotherapies have improved patient responses and survival, though not all patients benefit. Effective biomarkers may help to improve outcomes. Durvalumab is a human IgG1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and CD80, restoring antitumor immunity [1, 2]. PD-L1 expression on tumor or tumor-infiltrating immune cells measured manually with different immunohistochemistry (IHC) assays can enrich for patients responding to anti-PD-1/PD-L1 agents. Tumor-infiltrating cytotoxic CD8+ T cells may also have potential predictive utility for therapeutic response. We explored automated image analysis and pattern recognition of tumor biopsies to determine whether CD8+ and PD-L1+ cell densities could better identify patients most likely to respond to durvalumab than PD-L1 IHC alone. Methods CP1108/NCT01693562 was a nonrandomized phase I/II trial evaluating durvalumab in advanced NSCLC and other solid tumors [3]. By 29APR2016, 304 previously treated NSCLC patients, median 3 prior lines, received 10 mg/kg of durvalumab q2w ≤12 months. Baseline archived or fresh tumor biopsies were analyzed for PD-L1 (Ventana/SP263) and CD8 (Ventana/SP239) by IHC. For the marker combination, slides were scored using the product of PD-L1+ and CD8+ cell densities with Definiens’ Developer XD 2.1.4 software. For PD-L1 alone, ≥25% tumor cells stained for PD-L1 at any intensity were scored positive. Clinical outcomes (ORR, PFS and OS) were analysed based on CD8+ and PD-L1+ densities (n = 163 available) and PD-L1 alone in pre-treatment biopsies using a discovery (n = 84) and validation (n = 79) set. Datasets were matched on baseline PD-L1 status, histology, ECOG, lines of therapy, and response. Results Patients with high pretreatment CD8+ and PD-L1+ densities (prevalence = 36%) had better ORR, OS, and PFS compared to those with low CD8+ and PD-L1+ densities (Fig. 1), as well as high PD-L1 expression alone. Conclusions Automated image analysis of CD8+ and PD-L1+ cell densities in baseline tumor biopsies may identify patients with improved outcomes to durvalumab. Trial Registration ClinicalTrials.gov identifier NCT01693562. References 1. MedImmune/AstraZeneca. Data on file.2. Ibrahim R, Stewart R, Shalabi A: PD-L1 blockade for cancer treatment: MEDI4736.Semin Oncol 2015,42:474–483.3. Rizvi NA, Brahmer JR, Ou SHI, Segal NH, Khleif S, Hwu WJ, et al:Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1 antibody, in patients with non-small lung cancer (NSCLC).J Clin Oncol 2015,33(Suppl.):Abstract 8032.Fig. 1 (abstract O1).Clinical outcomes in CD8+/PD-L1+ or PD-L1 NSCLC patient subsetsClinical Trials: Cutting-Edge (Completed Trials)O2 Keynote-045: open-label, phase III study of pembrolizumab versus investigator’s choice of paclitaxel, docetaxel, or vinflunine for previously treated advanced urothelial cancerJoaquim Bellmunt,1 Ronald de Wit,2 David J Vaughn,3 Yves Fradet,4 Jae Lyun Lee,5 Lawrence Fong,6 Nicholas J Vogelzang,7 Miguel A Climent,8 Daniel P Petrylak,9 Toni K Choueiri,1 Andrea Necchi,10 Winald Gerritsen,11 Howard Gurney,12 David I Quinn,13 Stéphane Culine,14 Cora N Sternberg,15 Yabing Mai,16 Markus Puhlmann,16 Rodolfo F Perini,16 Dean F Bajorin171Dana-Farber Cancer Institute, Boston, MA, USA; 2Erasmus MC Cancer Institute, Rotterdam, Netherlands; 3Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 4CHU de Québec-Université Laval, Québec, QC, Canada; 5Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea; 6University of California, San Francisco, San Francisco, CA, USA; 7Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; 8Fundación Instituto Valenciano de Oncología, Valencia, Spain; 9Smilow Cancer Hospital at Yale University, New Haven, CT, USA; 10Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 11Radboud University Medical Center, Nijmegen, Netherlands; 12Westmead Hospital and Macquarie University, Sydney, NSW, Australia; 13Univeristy of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA, USA; 14Hôpital Saint-Louis, Paris, France; 15San Camillo Forlanini Hospital, Rome, Italy; 16Merck & Co., Inc., Kenilworth, NJ, USA; 17Memorial Sloan Kettering Cancer Center, New York, NY, USA Background There is no standard second-line therapy for advanced urothelial cancer. Although paclitaxel, docetaxel, and vinflunine are commonly used, they provide limited clinical benefit. KEYNOTE-045 compared the efficacy and safety of the anti–PD-1 antibody pembrolizumab versus investigator-choice chemotherapy as second-line therapy for advanced urothelial cancer that progressed or recurred following first-line platinum-based chemotherapy. Methods Eligible patients were enrolled regardless of PD-L1 expression and randomized 1:1 to pembrolizumab 200 mg Q3W for 24 months or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Randomization was stratified by ECOG PS (0/1 vs 2), liver metastases (yes vs no), hemoglobin level (<10 vs ≥10 g/dL), and time from last chemotherapy dose (<3 vs ≥3 months). The study had a group sequential design to control for type I error. Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review). ORR was a key secondary endpoint. Differences in OS and PFS were assessed in the intention-to-treat population using the stratified log-rank test Results Between November 5, 2014 and November 13, 2015, 542 patients from 29 countries were enrolled: 270 in the pembrolizumab arm, 272 in the chemotherapy arm. As of September 7, 2016, median follow-up was 9.0 months; 49 (18.4%) patients remained on pembrolizumab and 3 (1.2%) patients remained on chemotherapy. Baseline characteristics were generally balanced between arms, with 87.3% with visceral disease, 34.3% with liver metastases, 1.1% with ECOG PS 2, 81.5% with hemoglobin ≥10 g/dL, and 38.2% with <3 months since most recent chemotherapy. Pembrolizumab significantly improved OS over chemotherapy (HR 0.73, P = 0.0022; median 10.3 vs 7.4 months) (Table 1). There was no difference in PFS (HR 0.98, P = 0.42) (Table 1). ORR was significantly improved with pembrolizumab (21.1% vs 11.4%) (Table 1). Pembrolizumab was associated with fewer any-grade (60.9% vs 90.2%) grade 3-5 treatment-related AEs (15.0% vs 49.4%). 4 patients in each arm died due to treatment-related AEs. Conclusions Pembrolizumab demonstrated a statistically significant OS benefit over chemotherapy in the second-line advanced urothelial cancer setting, making it the first therapy to demonstrate a survival benefit over an active comparator in this population. The superior OS combined with the lower rate of any-grade and high-grade treatment-related AEs support pembrolizumab as a new standard of care for advanced urothelial cancer that progressed on/after platinum-based chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT02256436Efficacy in KEYNOTE-045End pointPembrolizumabN = 270ChemotherapyN = 272OS, no. of events155179 Median (95 % CI), months10.3 (8.0-11.8)7.4 (6.1-8.3) HR (95 % CI)0.73 (0.59-0.91); P = 0.0022PFS, no. of events218219 Median (95 % CI), months2.1 (2.0-2.2)3.3 (2.3-3.5) HR (95 % CI)0.98 (0.81-1.19); P = 0.42ORR (95 % CI)21.1 % (16.4-26.5)11.4 % (7.9-15.8) Treatment difference, % (95 % CI)9.6 (3.5-15.9); P = 0.0011O3 Efficacy and safety of nivolumab plus ipilimumab in metastatic urothelial carcinoma: first results from the phase I/II CheckMate 032 studyPadmanee Sharma1, Margaret K Callahan2, Emiliano Calvo3, Joseph W Kim4, Filipo de Braud5, Patrick A Ott6, Petri Bono7, Rathi N Pillai8, Michael Morse9, Dung T Le10, Matthew Taylor11, Pavlina Spilliopoulou12, Johanna Bendell13, Dirk Jaeger14, Emily Chan15, Scott J Antonia16, Paolo A Ascierto17, Delphine Hennicken18, Marina Tschaika18, Alex Azrilevich18, Jonathan Rosenberg21University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3START Madrid, Centro Integral Oncológico Clara Campal, Madrid, Spain; 4Yale Cancer Center, New Haven, CT, USA; 5Istituto Nazionale dei Tumori-Università degli Studi di Milano, Milano, Lombardia, Italy; 6Dana-Farber Cancer Institute, Boston, MA, USA; 7Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 8Emory Winship Cancer Institute, Atlanta, GA, USA; 9Duke University Medical Center, Durham, NC, USA; 10Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; 11Oregon Health & Science University, Portland, OR, USA; 12Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; 13Sarah Cannon Research Institute and Department of Medical Oncology, Tennessee Oncology, Nashville, TN, USA; 14Heidelberg University Hospital, Heidelberg, Baden-Wurttemberg, Germany; 15Vanderbilt-Ingram University Medical Center, Nashville, TN, USA; 16H. Lee Moffitt Cancer Center, Tampa, FL, USA; 17Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, Napoli, Italy; 18Bristol-Myers Squibb, Princeton, NJ, USACorrespondence: Padmanee Sharma (padsharma@mdanderson.org) Background Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor associated with clinical benefit in previously treated patients with metastatic urothelial carcinoma [1]. Preclinical and clinical data indicate that the combination of nivolumab plus ipilimumab,