Mersana's lead product candidate, upifitamab rilsodotin (UpRi), is a Dolaflexin ADC targeting NaPi2b and is being studied in UPLIFT, a single-arm registration strategy, in patients with platinum . CONFIDENTIAL Responses with XMT-1536 (UpRi) Occur Early and Appear to Deepen Over Time Change from Baseline in Target Lesions in Patients with Ovarian Cancer (n = 45) H = Higher NaPi2b Expression; L = Lower NaPi2b . Found inside – Page 38... against ovarian cancer and non-small-cell lung cancer (NSCLC) [5]. Although NaPi2b is overexpressed in these two indications, it is also expressed in ... [1] "These data further support the continued development of XMT-1536, our first-in-class Dolaflexin ADC targeting NaPi2b, which has recently been granted U.S. Food . Clinical trials.gov: With the identification of NaPi2b as the molecular target of mAb MX35, it became evident that the MX35 antigen is not only expressed in ovarian cancers but also in a series of other epithelial cancers, including lung cancer, thyroid cancer and renal cancer, potentially expanding the therapeutic application of the MX35 antibody to these and other types of cancer. 2020 Sep;158(3):631-639. doi: 10.1016/j.ygyno.2020.05.039. A wide range of novel therapeutic targets now present themselves for clinical evaluation and initial results are certainly encouraging. In this text, all these areas are covered by experts in the field. XMT-1536 utilizes the Dolaflexin platform to deliver 10-12 DolaLock auristatin payload molecules per antibody. EOC is the . 2012 Feb 27 [updated 2012 May 31]. These organisms thus produce substances containing novel chemotypes that may have beneficial effects for humans. As collection methods improve and new screen EOC is the most prevalent type of ovarian cancer (90%), and consists of five pathological subtypes: serous, mucinous, clear cell, endometrioid and undifferentiated carcinoma [ 11 ]. 2021 Mar 9;14(1):42. doi: 10.1186/s13048-021-00790-4. ​This SpringerBrief sheds new light on bioactive materials from marine extremophiles. Pre-clinical studies in an ovarian . Prevention and treatment information (HHS). The decreased expression level of the phosphate transporter NaPi2b in patients who had received neoadjuvant therapy can serve as a marker for monitoring the course of the disease and an indicator of the appointment of targeted therapy against the NaPi2b transporter, including monoclonal antibodies, which are in clinical trials for the treatment of ovarian cancer . This book provides the reader with a comprehensive understanding of both the basic principles and the clinical applications of nuclear oncology imaging techniques. Found insideUsing a case-based approach, the book provides clinical scenarios that include relevant accompanying radiology and pathology. Curr Oncol Rep. 2021 Jun 14;23(8):89. doi: 10.1007/s11912-021-01080-4. PLoS One. Found inside – Page 564MX35 recognises the sodium-dependent phosphate transport protein 2b (NaPi2b) which is overexpressed in more than 90 % of human ovarian epithelial cancers ... 2017 May 2;17(1):303. doi: 10.1186/s12885-017-3289-2. Found inside – Page 140NaPi2b is a sodiumdependent phosphate transporter and is expressed in about 90% of ovarian cancer. Ninety-five patients with platinum-resistant ovarian ... In the tumor images, insets are enlarged to show staining detail. The human sodium-dependent phosphate trans-port protein 2b — NaPi2b, (NPTIIb, NAPI-3B, FLJ90534, NAPI-IIb) or solute carrier family 34 mem-ber 2 is a transmembrane protein with at least eight highly hydrophobic helical regions that form channel structure via homodimeric assembly [1, 2]. 50% of patients with higher NaPi2b expression are ongoing in the study while only 33% of patients with lower Napi2b expression are ongoing in study. 2020 Jul;9(13):4756-4767. doi: 10.1002/cam4.3078. o: The Company expects to define the patient selection strategy based on the total data set from patients treated with XMT-1536 . Recent studies have shown that NaPi2b expression is enriched in the EGFR and KRAS mutant subtypes of lung adenocarcinoma. UPLIFT will enroll approximately 180 patients with platinum-resistant advanced ovarian cancer to obtain approximately 100 patients with higher NaPi2b expression. XMT-1536 is being evaluated in patients (pts) with ovarian cancer and non-small cell lung adenocarcinoma in a phase I study (NCT03319628) and has shown a favorable safety profile and evidence of clinical activity. Van Campenhout R, Muyldermans S, Vinken M, Devoogdt N, De Groof TWM. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. Found insideThis book provides a comprehensive overview of contemporary evidence-based management of urothelial carcinoma. For the whole cohort, high level expression was associated with improved overall survival. - Initiated UPLIFT single-arm registration strategy for evaluation of UpRi in platinum-resistant ovarian cancer- Ended first quarter of 2021 with $228 million in cash CAMBRIDGE, Mass., May 10, 2021 (GLOBE NEWSWIRE) -- Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting . 2017 Feb 2;8(2):e2581. Ovarian Cancer Patient-Derived Xenograft Models. Background: XMT-1536 is a first-in-class ADC targeting the sodium-dependent phosphate transport protein NaPi2b, broadly expressed in NSCLC and ovarian cancer. OncologyPRO is the home of ESMO's educational & scientific resources, with exclusive content for ESMO members such as ESMO's Congresses webcasts, This study investigates NaPi2b expression in NSCLC emphasising correlations to histology. There was a similar, but non-significant, trend for high level expression in adenocarcinoma cases to be associated with improved survival, which appeared to be the case for both high risk and good risk adenocarcinoma subtypes. There is no exclusion for patients with baseline peripheral neuropathy. Response - Ovarian Cancer N=20* All: Higher NaPi2b o: Lower NaPi2b oo: NaPi2b Not Yet Determined: N: 20: 14: 4: 2: CR: 2 (10%) 2 (14%) 0 (0%) 0 (0%) PR: 5 (25%) 2 (14%) 1 (25%) 2 (100%) uPR** 1 (5 . Found inside – Page iiThis book examines in depth the evidence, clinical applications and potential cancer signatures in the circulation and discusses alterations in circulating cell-free nucleic acids, and circulating tumor DNA, as well as the epigenome, genome ... The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). 2013 Oct 23;8(10):e77121. There were no significant differences in expression considering stage, primary tumour diameter, FEV1 (% predicted) or level of PD-L1 expression. Copyright © 2021 by the American Association for Cancer Research. H-score 290. GAPDH was used as loading control. A clinical trial of the NaPi2b . EOC is the . Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis. ovarian cancer (prOC, >60% with assumptions for an expression level cutoff in future development) and non-small cell lung cancer (NSCLC, ~60-80%). Cancer Res. 2020 Aug 9;12(8):2223. doi: 10.3390/cancers12082223. While normal ovary has been reported to lack expression of NaPi2b the expression is high in epithelial ovarian cancer (EOC) NaPi2b is expressed in 80-100% of the tumors [3, 5, 6, 9, 10]. This is a multi-center study of XMT-1536 (upifitamab rilsodotin) in patients with tumors likely to express NaPi2b, focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer, adenocarcinoma subtype. UPLIFT will evaluate the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy. factor, and NaPi2b are common antigens used for conjugation in this malignancy, as they are usually overexpressed in epithelial ovarian cancer [12]. The median duration of response was not yet reached in the 7 patients with ovarian cancer with higher NaPi2b expression. This site needs JavaScript to work properly. 2016 Jun;21(1-2):25-40. doi: 10.1007/s10911-015-9349-9. Despite high levels of expression in normal lung of non-human primate, the crossreactive ADC exhibited an acceptable safety profile with a dose-limiting toxicity unrelated to normal tissue target . Tumor tissue will be retrospectively evaluated for NaPi2b expression. Overall high NaPi2b was seen in 56/95 (59%) with poor risk adenocarcinoma subtypes (micropapillary, solid, mucinous) and 71/106 (67%) with good risk subtypes (papillary, acinar, lepidic). On multivariable analysis, NaPi2b remained the strongest predictor of improved survival (HR 0.77, 95% CI 0.58 - 1.02, p=0.07), though stage remained the only statistically significant variable. Abstract A043: NaPi2b expression in a large surgical non-small cell lung cancer cohort, Abstract PL04-02: Extracellular vesicles as opportunities for integrative or focused liquid biopsy studies, Abstract A046: Pre-clinical assessment of neratinib sensitivity and biomarkers of response, Abstract A053: Significance of Transglutaminase 2 expression on clinical outcome in metastatic renal cell carcinoma, Abstract A028: Clinical and analytic validation of FoundationOne CDx™ for, Abstract A036: Identification of secretome-based eribulin biomarkers for breast cancer therapeutics, Abstract A032: Clinical significance of vimentin-positive AXL-expressing circulating tumor cells in advanced non-small-cell lung cancer patients, Biomarkers: Poster Presentations - Proffered Abstracts, Cancer Epidemiology, Biomarkers & Prevention, Patient-Focused Therapies in Breast Cancer. Mersana's second product candidate targeting NaPi2b-expressing tumors, XMT-1592, is an ADC created using Mersana's customizable and . Results: We show here that an anti-NaPi2b ADC is effective in mouse ovarian and NSCLC tumor xenograft models and well-tolerated in rats and cynomolgus monkeys at levels in excess of therapeutic doses. Found inside – Page 72“To better understand the expression of this protein in different histologic types of ovarian carcinomas, we immunostained 50 tumor samples with anti-NaPi2b ... For IHC, TMAs were stained with an anti-human NaPi2b primary antibody (MERS67) on the Leica Bond RX auto-stainer and the H-score (0 – 300) calculated based on the percentage of tumour cells stained multiplied by the staining intensity (0 - 3+). Updated interim safety, tolerability, and efficacy data for the ovarian cancer cohort of the ongoing expansion portion of the Phase I study evaluating XMT-1536 show a 34% objective response rate (ORR) and 79% disease control rate, including two complete responses. Aim: To study the expression profile of the NaPi2b protein and its localization in breast, ovarian and lung cancer cells in relation to normal tissues adjacent to tumor. MeSH Li XR, Zhu Y, Zhang GN, Huang JM, Pei LX. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. ovarian cancer showed proper targeting, with tumor to normal tissue uptake ratios ranging from 2.3:1 to 34:1 (mean 10.18:1) [11]. This book will provide readers with a practice-based approach to all aspects of clinical nephrology. Abstracts: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26-30, 2019; Boston, MA Background: NaPi2b (SLC34A2) is a sodium-dependent phosphate transporter expressed in a high proportion of non-small cell lung cancer (NSCLC), especially adenocarcinoma, and ovarian carcinoma cases, as well as other tumour types. Moore KN, Birrer MJ, Marsters J, Wang Y, Choi Y, Royer-Joo S, Lemahieu V, Armstrong K, Cordova J, Samineni D, Schuth E, Vaze A, Maslyar D, Humke EW, Hamilton EP, Liu JF. •XMT-1536 data were last presented at the American Society of . Bookshelf More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov (NCT03319628). Cell Death Dis. A Molecular View of Pathological Microcalcification in Breast Cancer. Different staining intensities were observed in different grades of epithelial ovarian cancer. Would you like email updates of new search results? Na/Pi-cotransport via NaPi2b . NaPi2b expression in ovarian cancer (A), fallopian tube epithelium (B), normal bronchial epithelium (solid arrow) adjacent to NaPi2b-staining lung adenocarcinoma (open arrow; C), and type 2 pneumocytes in lung parenchyma (D). Epub 2020 May 5. Selecting the correct antigen is a crucial step for e ectiveness, and many e orts have been developed to identify novel antigens. 2020 Jan 15;26(2):364-372. doi: 10.1158/1078-0432.CCR-18-3965. XMT-1536 is in Phase 1 clinical trials in patients with tumors expressing NaPi2b, including ovarian cancer and NSCLC adenocarcinoma. Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, Scambia G, Engelholm SA, Joly F, Weber D, El-Hashimy M, Li J, Souami F, Wing P, Engelholm S, Bamias A, Schwartz P. J Clin Oncol. The median duration of response was not yet reached in the 7 patients with ovarian cancer with higher NaPi2b expression. Progress in Gynecologic Cancers with Antibody Drug Conjugates. Immunohistochemical and mRNA expression data . A clinical trial of the NaPi2b-targeting antibody drug conjugate XMT-1536 is currently underway (NCT03319628). Aim: Privacy, Help Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Found inside – Page 4947In vivo PTH provokes apical NHE3 and NaPi2 redistribution Expression of GABA ... in brown adipose tissue Ovarian cancer - associated lymphocyte recognition ... Found inside – Page 303TAG-72 expression has been shown in the majority of ovarian carcinomas tested (27) ... as the sodium–dependent phosphate transport protein 2b (NaPi2b) (55). As part of its diagnostic development plan, the Company evaluated TPS methodology in the expansion portion of the Phase 1 study in ovarian cancer and demonstrated that TPS captures a broad . The investigational antibody-drug drug, being developed by Mersana Therapeutics, targets NaPi2b, a multi-transmembrane sodium . Intensity of NaPi2b protein expression was calculated with semiquantitative scores. While normal ovary has been reported to lack expression of NaPi2b the expression is high in epithelial ovarian cancer (EOC) NaPi2b is expressed in 80-100% of the tumors [3, 5, 6,9,10]. Considering adenocarcinoma subtypes, high NaPi2b was seen with 18/21 (86%) micropapillary, 35/61 (57%) solid, 3/13 (23%) mucinous, 54/84 (64%) acinar, 8/13 (62%) papillary, 9/9 (100%) lepidic and 3/9 (33%) adenosquamous. Privacy, Help Found insideOvarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines ... Background: XMT-1536 is a first-in-class ADC targeting the sodium-dependent phosphate transport protein NaPi2b, broadly expressed in NSCLC and ovarian cancer. The study consists of three segments: dose escalation (DES . Careers. Rebmab200, a humanized monoclonal antibody targeting the sodium phosphate transporter NaPi2b displays strong immune mediated cytotoxicity against cancer: a novel reagent for targeted antibody therapy of cancer. The Company expects to provide an update on the ovarian cancer expansion cohort this year. NaPi2b on lung cancer cells, as well as its overexpression on ovarian cancers, compelled us to assess it as an ADC target. Epub 2020 Jun 11. To date, the studies on NaPi2b/MX35 expression in different histological types of EOC are limited. Methods: Prevention and treatment information (HHS). Although comparable amounts of NaPi2b were expressed on the cell surface of the OVCAR3 and Igrov1 cell lines, the OVCAR3 appeared to be more sensitive to the ADC ( Fig. Found insideThis volume, in discussing resistance to ibritumomab, will focus on the mechanism, hematological aspects, radiological and nuclear medicine aspects, and medical physics that deal with radiation dosimetry, and will outline future prospects ... high proportion of Non-Small Cell Lung Cancer (NSCLC), especially adenocarcinoma, and ovarian carcinoma cases, as well as some other tumour types. Citation Format: Paul L Mitchell, Hui Yu, Gareth Rivalland, Khashayar Asadi, Rebecca Mosher, Fred Hirsch, Christopher Rivard. This book is a printed edition of the Special Issue "Marine Compounds and Cancer" that was published in Marine Drugs In the dose-escalation portion of the Phase I study (NCT03319628), XMT-1536 showed clinical activity at doses >20mg/m 2 . This volume presents 30 state-of-the-art protocols and reviews to set up and apply primary hepatocyte cultures for research and screening purposes.
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