PURPOSE Activation of STING (Stimulator of INterferon Genes) can trigger a robust, innate anti-tumor immune response in immunologically "cold" tumors such as glioblastoma. EXPERIMENTAL DESIGN A small-molecule STING agonist, IACS-8779, was stereotactically administered using intraoperative navigation intratumorally in dogs with spontaneously arising glioblastoma. The phase I trial used an escalating dose design, ascending through four dose levels (5µg - 20µg). Treatment was repeated every 4-6 wee...
PURPOSE The epigenetic mechanisms involved in transcriptional regulation leading to malignant phenotype in gliomas remains poorly understood. Topoisomerase IIB (TOP2B), an enzyme that de-coils and releases torsional forces in DNA, is over-expressed in a subset of gliomas. Therefore, we investigated its role in epigenetic regulation in these tumors. EXPERIMENTAL DESIGN To investigate the role of TOP2B in epigenetic regulation in gliomas, we performed paired ChIP-seq for TOP2B and RNA-seq analysis...
Purpose: Selective RAF-targeted therapy is effective in some patients with BRAFV600E mutated glioma, though emergent and adaptive resistance occur through ill-defined mechanisms. Experimental Design: Paired pre-/ post- RAF inhibitor (RAFi)-treated glioma samples (N=15) were obtained and queried for treatment-emergent genomic alterations using DNA and RNA sequencing. Functional validation of putative resistance mechanisms was performed using established and patient-derived BRAFV600E-mutant glioma...
Last. Brigette B Y Ma(CUHK: The Chinese University of Hong Kong)H-Index: 59
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Background: No standard treatment exists for platinum refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an anti-programmed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. Patients and methods: Patients with non-keratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 week...
Purpose null Data are sparse for oral selective estrogen receptor (ER) degraders (SERDs) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study. null Materials and methods null A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; n=77) or with ribociclib (arm B; n=78) or alpelisib (arm C; n=43) in heavily pretreated adults with histologically confirmed ER-positive breast cancer and pri...
#2Brett L. Ecker(MSK: Memorial Sloan Kettering Cancer Center)
Last. Kevin C. Soares(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 3
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Background: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management. Methods: The hidden genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA sequencing d...
PURPOSE Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide (LEN), demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, Phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historical control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination. EXPERIMENTAL DESIGN Data were ...
Purpose: There is still no standard non-surgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any chondrosarcomas have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor. Experimental Design: We obtained 98 newly diagnosed CHS fresh tumors from multi-institutions and performed comprehensive analysis of data from CyTOF, whole exome sequencing, and flowcytometry in 22 cases. Clinical data from...
Purpose: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e. 150-200/year) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKIs). Lack of human models for any SDH-mutant tumors, including GI...
Purpose null To evaluate drug-drug interactions between the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole. null Experimental design null Patients with HER2-expressing advanced solid tumors were enrolled in this phase I, open-label, single-sequence crossover study (NCT03383692) and received intravenous T-DXd 5.4 mg/kg every 3 weeks. Patients received ritonavir (cohort 1) or itracon...