tbuckley/cabot-search huggingface dataset:
Integration of the Cancer-Related Pro-Inflammatory Response as a Stratifying Biomarker of Survival Benefit with Sorafenib in Hepatocellular Carcinoma
Authors: J. Howell, D. Pinato, R. Ramaswami, T. Arizumi, C. Ferrari, A. Gibbin, M. Burlone, G. Guaschino, J. Black, L. Sellers, M. Kudo, M. Pirisi, R. Sharma
Journal: Journal of Hepatology (2016)
C-Edge Head-to-Head: Efficacy and Safety of Elbasvir and Grazoprevir Compared with Sofosbuvir/Pegylated Interferon/Ribavirin: A Phase 3 Randomized Controlled Trial
Authors: J. Sperl, G. Horvath, W. Halota, J.A. Ruiz-Tapiador, A. Streinu-Cercel, L. Jancoriene, K. Werling, H. Kileng, S. Koklu, J. Gerstoft, S. Patel, J. Qiu, E. Assante-Appiah, J. Wahl, B.-Y. Nguyen, E. Barr, H.L. Platt
Journal: Journal of Hepatology (2016)
Sixty seconds on . . . sex education
Authors: Anne Gulland
Journal: BMJ (2016)

Yes, parents around England will be rejoicing at the news that the education secretary, Justine Greening, is considering compulsory sex education for all secondary school children. This comes just a few months after the previous education secretary, Nicky Morgan, declared the opposite, despite pleas from the parliamentary education, health, home affairs, and business select committees, as …
Histology obtained by needle biopsy gives additional information on the prognosis of hepatocellular carcinoma
Authors: Hannah van Malenstein, MIna Komuta, Chris Verslype, Vincent Vandecaveye, Ben Van Calster, Baki Topai, Wim Lalemon, David Cassiman, Werner Van Steenbergen, Raymond Aerts, Dirk Vanbeckevoort, Didier Bielen, Jacques Pirenne, Jos van Pelt, Tania Roskams, Frederik Nevens
Journal: Hepatology (2011)
RETRACTED: PS 124 - Efficacy and Safety of Induction Dosing of Vedolizumab for Reducing Biliary Inflammation in Primary Sclerosing Cholangitis (Psc) in Individuals with Inflammatory Bowel Disease
Authors: B. Eksteen, J. Heatherington, J. Oshiomogo, R. Panaccione, G. Kaplan, S. Ghosh
Journal: Journal of Hepatology (2016)
Comparison of Short-Term Outcomes Between CSTIBES02 and ALL Ph08 Trials for Young Patients with Philadephia Chromosome-Positive ALL (Ph+ALL) Differing In Imatinib Dose and Amount of Chemotherapy Before Stem Cell Transplantation
Authors: Josep-Maria Ribera, Olga Garcia, Pau Montesinos, Manuel Barrios, Albert Oriol, Salut Brunet, Jose Gonzalez, Jordi Esteve, Mar Tormo, Eloy Del Potro, Maria-José Moreno, Pascual Fernández-Abellán, Jesú S. M.a Hernández-Rivas, Pere Barba, Josep Sarrá, Eugènia Abella, Maria-Teresa Bernal, Andreu Llorente, Maria-Luz Amigo, Esperanza Lavilla, Pilar Bravo, Miguel-Angel Sanz, Evarist Feliu
Journal: Blood (2011)
Dxn Veris System for HCV Viral Load Monitoring in the Era of Second wave Direct-Acting Antiviral Agents
Authors: V. Micheli, A. Lombardi, A. Mancon, D. Mileto, N. Zanchetta, C.F. Magni, L. Milazzo, E. Angeli, G. Gubertini, M. Galli, M.R. Gismondo
Journal: Journal of Hepatology (2016)
Thymidylate synthase (TS) expression as a prognostic molecular marker in stage II/III colon cancer.
Authors: Dirk Klingbiel, Edoardo Missiaglia, Pu Yan, Sabine Tejpar, Arnaud Roth, Giovanni d'Ario, Mauro Delorenzi, Fred Bosman
Journal: Journal of Clinical Oncology (2013)

3577 Background: Studies on the association between colorectal cancer (CC) outcome and thymidylate synthase expression have provided inconsistent results. In this study we attempted to resolve the issue by assessing the associations between TS expression and outcome in a population of primary CC patients (pts), who after resection were randomized to 5-FU/FA vs. FOLFIRI adjuvant therapy. Methods: Immunohistochemical staining for TS protein was successfully performed for 1211 pts in the PETACC3 trial. TS immunoreactivity was scored as high expression (≥75% positive) and low expression (&lt;75% positive). Gene expression respectively copy number data were available for 853 respectively 306 of these samples. Twelve single nucleotide polymorphisms (SNPs) close to the TYMS gene were assessed in 923 pts. Association of variables with relapse-free (RFS) and overall survival (OS) was assessed using Cox regression models. Results: High TS expression and RNA level were strongly associated (log fold change 0.65, p&lt;0.001). Both were significantly higher in proximal CC. As expected, both were associated with other characteristics of proximal CC: MSI, BRAF mutation, high tumor grade. RNA was significantly correlated with gene copy number, distal CC showing more frequent allelic loss. Three SNPs were associated with gene expression which was validated in data from the 1000 genomes project, but none with survival. High TS expression was more strongly associated with better OS in pts receiving FOLFIRI (HR 0.4, 95% CI 0.3–0.6, p&lt;0.001), than 5-FU/FA (HR 0.8, 95% CI 0.5–1.1, p=0.13), with a significant interaction (p=0.05). Similar results were observed for RFS (HR 0.5, p&lt;0.001 vs. HR 0.7, p=0.07; interaction p=0.11). TS expression is still highly prognostic in multivariate models adjusting for factors associated with risk or proximal tumors in FOLFIRI treated pts (OS: HR 0.5, p=0.008; RFS: HR 0.6, p=0.02), but not in F-FU/FA treated pts (OS and RFS: HR=1, p=1). Conclusions: TS expression is lower in distal CC, partly due to deletion of the TYMS locus. Pts with high TS expression have longer RFS and OS, notably when treated with FOLFIRI. For these pts addition of irinotecan to 5-FU/FA adjuvant chemotherapy might be considered. Clinical trial information: NCT00026273.
Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria
Authors: Nicholas J. White, Tran T. Duong, Chirapong Uthaisin, François Nosten, Aung P. Phyo, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Podjanee Jittamala, Kittiphum Chuthasmit, Ming S. Cheung, Yiyan Feng, Ruobing Li, Baldur Magnusson, Marc Sultan, Daniela Wieser, Xiaolei Xun, Rong Zhao, Thierry T. Diagana, Peter Pertel, F. Joel Leong
Journal: New England Journal of Medicine (2016)

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites.
Single-nucleotide polymorphisms (SNPs) of CYP19A1 and plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment.
Authors: G. Lunardi, S. Lastraioli, P. Bruzzi, P. Pronzato, G. Bisagni, R. Ponzone, M. Porpiglia, S. Russo, L. Del Mastro, M. Venturini
Journal: Journal of Clinical Oncology (2010)

2606 Background: The efficacy of aromatase inhibitors in breast cancer patients might be related to various SNPs of CYP19A1 gene (encoding aromatase enzyme), determining a different suppression of ES. Methods: We evaluated the long-term suppression (up to 12 months) of plasma ES levels following L (25mg/d) treatment according to 4 SNPs of CYP19A1 (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G). Patients were enrolled into a prospective, Italian multicenter clinical trial (GIM5). Blood samples were obtained into EDTA vials immediately before (n=204) L therapy and at 6 wks (n=180), 6 months (n=152) and 12 months (n=136) during L treatment. SNPs were identified from DNA obtained from peripheral blood cells by Hexaprimer Amplification Refractory Mutation System PCR (H-ARMS-PCR). Plasma ES levels were evaluated by Radio Immuno Assay (RIA). Results: No association (all p values >0.15) between CYP19 genotypes and ES plasma concentrations (log-transformed) was seen, either at baseline or at 6 wks, 6 and 12 months (the latter 3 analyses were replicated with or without adjustment for baseline levels). During L treatment, ES concentrations ([ES]) were exponentially correlated to baseline ES values ([ES6wks]=3.84*[ESBas](0.401); [ES6mos]=1.831*[ESBas](0.535); [ES12mos]=4.482*[ESBas](0.285)). Circulating [ES] during L treatment showed a trend toward lower values with the long duration of the therapy (n=107; median [ES6wks]=52 pg/mL; [ES6mos]=44 pg/mL; [ES12mos]=36 pg/mL). Conclusions: Both baseline and during L therapy circulating ES levels did not seem to be associated with genetic variation at the CYP19A1 locus. Notwithstanding the high variability and the residual correlation with baseline values, the proportional reduction in circulating ES concentrations during L treatment increased with increasing baseline values, allowing a marked ES suppression in most patients. The aromatase inhibition seemed to increase with the continuation of L treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
P1312 : Alfapump system versus transjugular intrahepatic portosystemic shunt and paracentesis in the treatment of ascites. A multicentre randomised controlled study (AGUA-trial)
Authors: C. Engelmann, O. Brosteanu, H. Tenckhoff, J. Babatz, F. Lammert, M. Manns, I. Schiefke, T. Bruns, C. Trautwein, S. Zeuzem, U. Treichel, R. Jalan, T. Berg
Journal: Journal of Hepatology (2015)
Maintenance of Quality of Life in Patients with Malignant Ascites During Treatment with the Trifunctional Antibody Catumaxomab: Results from the Phase III B Casimas Trial
Authors: F. Lordick, J. Sehouli, I.B. Vergote, P. Rosenberg, A. Schneeweiss, A. Block, C. Salat, G. Scambia, D. Berton-Rigaud, P. Wimberger
Journal: Annals of Oncology (2012)
The Intra-Tumor Heterogeneity of C19MC miRNA Cluster Expression Mirrors the Presence of the Side Population in Hepatocellular Carcimnoa
Authors: F. Colombo, C. Augello, A. Terrasi, E. Trombetta, M. Maggioni, M. Baccarin, R. Silipingi, S. Guerneri, S. Bosari, L. Porretti, V. Vaira
Journal: Journal of Hepatology (2016)
Rotational Thromboelastometry and Child can Predict 3-Month Mortality in Liver Cirrhosis
Authors: S. BedreIi, J.-P. Sowa, S. Blomeyer, S. Malek, G. Kneiseler, L. Bechmann, A. Paul, G. Gerken, D. Heider, F. Saner, A. Canbay
Journal: Journal of Hepatology (2016)
Sofosbuvir-Based, Ribavirin-Free Regimens in Patients with Chronic Hepatitis C and End-Stage Renal Disease: A Look at Safety, Tolerability and Efficacy
Authors: H.E. Nazario, A. Modi, M. Ndungu, R. Ramirez, L. Tujague, J. Weinstein
Journal: Journal of Hepatology (2016)
Higher Serum Bilirubin Levels of Living Liver Donors may be Associated with Decreased Risk of Post-Transplant Hepatocellular Carcinoma Recurrence
Authors: S. Han, J.D. Yang, D.H. Sinn, J. Ko, J.M. Kim, J.C. Shin, H.J. Son, J.-W. Joh, G. Kim
Journal: Journal of Hepatology (2016)
Correlation Between Severity of cGvHD and Transplant Outcome: A Retrospective Monocenter Study Based on NIH Classification,
Authors: Colombe Saillard, Roberto Crocchiolo, Sabine Furst, Jean El-Cheikh, Luca Castagna, Claire Oudin, Catherine Faucher, Lemarie Claude, Christian Chabannon, Angela Granata, Didier Blaise
Journal: Blood (2011)
Recombinant Human Thrombomodulin in the Treatment of Acute Myeloid Leukemia Patients Complicated By Disseminated Intravascular Coagulation: Results of a Multicenter, Retrospective Epidemiologic Study in Japan
Authors: Naoki Takezako, Naohiro Sekiguchi, Satoshi Noto, Yoshitaka Ogino, Akiyoshi Miwa, Takayuki Ikezoe
Journal: Blood (2014)
Neuropathy in Multiple Myeloma Patients Treated with Bortezomib: A Multicenter Experience.
Authors: Tommaso Caravita, Maria Teresa Petrucci, Alessandra Spagnoli, Agostina Siniscalchi, Massimo Offidani, Vincenzo Federico, Patrizia Falco, Manuela Rizzo, Antonio Palumbo, Paolo de Fabritiis
Journal: Blood (2007)
Treatment with Sofosbuvir + Simeprevir for 12 Weeks in HCV Compensated Cirrhosis (Genotypes 1 and 4); The Use of Ribavirin Does Not Influence Sustained Viral Response
Authors: A. Gallego, E. Alvarado, C. Gely, N. Pagès, M. Masip, N. Margall, X. Torras, C. Guarner
Journal: Journal of Hepatology (2016)
Combining IIb/IIIa Inhibition and Heparin for Acute Coronary Syndromes: Evidence of a Gradient for Bleeding Hazard from the PARAGON Randomized Factorially Designed Trial
Authors: RA Harrington, LK Newby, DJ Moliterno, MV Bhapkar, PW Armstrong, RJ Simes, HD White, Frans Van de Werf, A Rames, EJ Topol
Journal: Journal of the American College of Cardiology (1997)
Interim 18f-PDGPET for Aggressive Non-Hodgking's Lymphoma: A Systematic Review and Meta-Analysis
Authors: Domenica Caramazza, Francesco Dentali, Michele Merli, Giorgia Saccullo, Alessandra Malato, Gerlando Quintini, Emilio Iannitto, Francesco Passamonti, Sergio Siragusa
Journal: Blood (2011)
Sustained Virologic Response to Daclatasvir and Sofosbuvir, with or without Ribavirin, among Patients in the French Daclatasvir ATU Programme Infected with HCV Genotypes 4, 5 and 6
Authors: C. Hézode, A. Abergel, J. Chas, F. Conti, L. Cotte, M. Tateo, L. Alric, J. Vergniol, C. Tomei, P.-H. Bernard, V. Loustaud-Ratti, J.-P. Arpurt, D. Blaison, D. Larrey, L. Fedchuk, Y. Bennai, A. Filipovics, H. Fontaine, G.-P. Pageaux
Journal: Journal of Hepatology (2016)
Precore and Basal Core Promoter Mutants Improve the Diagnostic Performance of Fibroscan® or Fibrotest® to Predict Significant Fibrosis in Chronic Hepatitis B Patients
Authors: M. Lapalus, K.J. Nana, C. Laouenan, L. Larrouy, E. Estrabaud, M. Martinot-Peignoux, A. Marlu, J. Cronfalt, K. Appourchaux, N. Boyer, P. Bedossa, P. Marcellin, V. Leroy, T. Asselah
Journal: Journal of Hepatology (2016)
New way to define disease is needed to reduce overdiagnosis, experts agree
Authors: Susan Mayor
Journal: BMJ (2016)

A new process is needed for defining diseases that takes account of the potential risks of overdiagnosis and overtreatment as well as the benefits of appropriate diagnosis and care, researchers, policymakers, and consumer groups agreed at an international congress this week.

“The problem at the moment is that we don’t have an internationally agreed process,” said Paul Glasziou, professor of evidence based practice at Bond University, Robina, Queensland. “Disease definitions are developed on a very ad hoc basis, often by guideline panels making recommendations about tests and treatments who, along the way, incidentally change the definition of a disease,” he told the Preventing Overdiagnosis conference, co-sponsored by The BMJ and held on 20-22 September in Barcelona (www.preventingoverdiagnosis.net).

“We have a clear, internationally agreed process on what evidence is needed to recommend a particular treatment. But there has been a neglect of the fundamental issue that comes before that, which is the definition of disease.” 

He explained that the problem with expanding definitions of disease so …
Higher Genetic Barrier Revealed in HCV GT-1b/2/4/6 Subjects than GT-1a Patients – A Proof of Concept Trial of TG-2349 (Furaprevir)
Authors: C.-T. Yeh, S.-J. Hsu, T.-H. Hu, C.-J. Liu, C.-E. Tsai, C.-M. Chen, L.-W. Chang, C.-C. Lin, C.-H.R. King, M.-C. Hsu
Journal: Journal of Hepatology (2016)
Regenerate: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Multicenter Study of Obeticholic Acid Therapy for Nonalcoholic Steatohepatitis
Authors: V. Ratziu, A.J. Sanyal, L. MacConell, R. Shringarpure, T. Marmon, D. Shapiro, Z.M. Younossi
Journal: Journal of Hepatology (2016)
Abstract 3019: GIPC high expression rescues BRCA2 deficiency and promotes tumorigenesis
Authors: Xia Ding, Shyam K. Sharan
Journal: Cancer Research (2015)

Abstract Breast cancer is the most prevalent cancer in women worldwide and mutation in breast cancer susceptible gene 2 (BRCA2) is one of the genetic factors conferring highest risk (40-70%) of developing breast cancer. Although BRCA2 proteins are known to maintain genomic stability mainly by homologous recombination-mediated DNA repair, a detailed mechanism of how BRCA2 loss induces tumorigenesis remains unclear. Interestingly, BRCA2 null mice display embryonic lethality, while inactivation of both alleles of BRCA2 in tumor cells renders them able to survive and are predisposed to tumorigenesis only when there are mutations in BRCA2 genetic interactors. In the current study, we tried to identify such genes using a mouse embryonic stem cell (mESC)-based insertional mutagenesis screen. In mESCs with one knockout allele of Brca2 and the other allele flanked by loxP sites, cell death can be induced by Cre-mediated loss of the conditional allele. To identify genes whose up-regulation can rescue cell death induced by loss of BRCA2, we transduced these mESC with murine stem cell retrovirus (MSCV) expressing Cre recombinase. We obtained Brca2-null mESCs that were rescued by the viral insertion and used them to clone the viral insertion sites. We identified several candidate genes that were up-regulated in viable mESCs. One of these genes encodes a PDZ domain-containing protein, GIPC3, and expression of Gipc3 mRNA was elevated 3 to 4-fold in the rescued clone. We were able to rescue lethality of Brca2-null mESC by overexpressing GIPC3. The rescued cells lost RAD51 foci formation in response to irradiation and were hypersensitive to DNA damaging agents and exhibited an overall increase in genomic instability. Mechanistically, GIPC3 can bind to APPL1 and APPL2, two adaptor proteins involved in AKT-mediated cell survival pathway. We found an increased level of the active form of AKT in GIPC3-rescued cells, and a knock down of APPL1 and APPL2 blocked the rescue by GIPC3 overexpression. We found that the Gipc3 transgene can partially rescue the lethality of Brca2 null embryos and contribute to tumorigenesis in K14-Cre; Brca2cko/cko mice. Besides GIPC3, another GIPC family member, GIPC1 can also rescue BRCA2 loss-induced lethality in mESCs. Oncomine analysis showed Gipc2 mRNA up-regulation in BRCA1 deficient human breast tumors, suggesting the possibility that high expression of all the GIPC family members (GIPC1, 2 and 3) might facilitate BRCA1 or BRCA2-loss induced tumorigenesis. Citation Format: Xia Ding, Shyam K. Sharan. GIPC high expression rescues BRCA2 deficiency and promotes tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3019. doi:10.1158/1538-7445.AM2015-3019
Phosphatase and tensin homologue <i>(PTEN)</i> loss and response to phase I trials targeting PI3K/AKT/mTOR pathway in patients with advanced cancer.
Authors: I. Garrido-Laguna, F. Janku, A. Tsimberidou, J. Wheler, GS. Falchook, S. Fu, D.S. Hong, A. Naing, S. Piha-Paul, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

e13018 Background: PTEN loss has been reported in different tumor types and it leads to activation of the PI3K/AKT/mTOR pathway. Patients bearing tumors with PTEN loss may benefit from treatment with drugs targeting PI3K/AKT/mTOR pathway. Methods: Cytoplasmic PTEN protein expression was evaluated by immunohistochemistry using paraffin blocks from patients referred to the Phase I Unit at M. D. Anderson. Loss of PTEN was established when staining was positive in less than 10% of tumor cells. Patients with PTEN loss were selectively treated with regimens containing inhibitors of PI3K-AKT-mTOR pathway. Results: 159 samples from patients with various advanced cancers have been collected for analysis. The most frequent tumor histologies were colorectal (26), melanoma (23), ovarian (22), head and neck squamous cell carcinoma (13), breast (10), endometrial (8), NSCLC (8), and sarcoma (6). PTEN status was available for 61 patients at the time of submission. Twelve (20%) out of the 61 patients had loss of PTEN including endometrial cancer (3 out of 5, 60%), cervical cancer (2 out of 4, 50%), non-small cell lung cancer (1 out of 2, 50%), head and neck squamous cell carcinoma (2 out of 5, 40%), melanoma (3 out of 12, 25%), colon cancer (1 out of 8, 12.5%). Ten patients with PTEN loss are currently being treated on PI3K-AKT-mTOR pathway targeted phase I protocols. Eight patients have already been restaged. Five patients (63%) had tumor regression ranging from -16% to -70%. Two out of 8 (25%) patients have achieved partial response per RECIST criteria. Five out of 8 had stable disease. One patient had progressive disease. PFS for these patients are: +21, +19, +19, +13, +12, +9, +9 and 5 weeks. Conclusions: Preliminary analysis suggests that PTEN loss was detected in 20% of patients with different solid tumors. 63% of patients with PTEN loss had tumor regression when challenged with drugs targeting the PI3K-AKT-mTOR pathway. No significant financial relationships to disclose.
Relapse and Treatment-Emergent RAVS with DAA-Based Regimens in Hepatitis C Virus (HCV) Mono- or Human Immunodeficiency Virus (HIV)-HCV Co-Infected Patients – a Real Concern in Clinical Practice? Results from the German Hepatitis C Cohort (GECCO)
Authors: S. Christensen, P. Ingiliz, K. Schewe, J. Rockstroh, D. Hueppe, A. Baumgarten, T. Lutz, G. Schmutz, K.G. Simon, H. Busch, T. Kimhofer, S. Mauss
Journal: Journal of Hepatology (2016)
The Clinical Significance Of Diastolic Dysfunction On The Outcome After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Naoki Shingai, Kazuhiko Kakihana, Shuntaro Ikegawa, Yukie Takahashi, Jun Aoki, Kosuke Yoshioka, Kensuke Narukawa, Shinya Ishida, Aiko Igarashi, Takeshi Kobayashi, Noriko Doki, Ohashi Kazuteru, Hisashi Sakamaki
Journal: Blood (2013)
Multidrug-Related Protein 1 (MRP1) Polymorphisms rs129081, rs212090, and rs212091 Predict Survival In Acute Myeloid Leukemia
Authors: Desiree Kunadt, Christian Dransfeld, Maria Schmiedgen, Michael Kramer, Christoph Röllig, Christian Thiede, Martin Bornhaeuser, Ulrich Mahlknecht, Gerhard Ehninger, Markus Schaich, Friedrich Stölzel
Journal: Blood (2013)
Trop-2 as a therapeutic target for the antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132), in patients (pts) with previously treated metastatic small-cell lung cancer (mSCLC).
Authors: Alexander Starodub, D. Ross Camidge, Ronald J. Scheff, Sajeve Samuel Thomas, Michael J. Guarino, Gregory A. Masters, Kevin Kalinsky, Leena Gandhi, Aditya Bardia, Wells A. Messersmith, Allyson J. Ocean, Pius P Maliakal, Robert M. Sharkey, Francois Wilhelm, David M Goldenberg, Rebecca Suk Heist
Journal: Journal of Clinical Oncology (2016)

8559 Background: Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC. Therefore, the efficacy and safety of this new ADC is being examined in previously treated mSCLC. Methods: A Phase I/II clinical trial (ClinicalTrials.gov, NCT01631552) is enrolling mSCLC pts, administering IMMU-132 on days 1 and 8 of 21-day treatment cycles. Treatment continues based on tolerance or until progression, with safety and response assessments (RECIST 1.1) made every week and at 8-12 weeks, respectively. No prophylactic diarrhea or G-CSF medication is given. Results: Thirty-one mSCLC pts were enrolled by 11/19/15. Twenty-eight pts are assessable [median age 63 yrs, 10 M/18 F, ECOG 0 (N=5)/1 (N=23)], with a median of 2.5 (range: 1-5) prior chemotherapies. Pts were given IMMU-132 doses at 8 mg/kg (N=15) or 10 mg/kg (N=13). All pts had previous treatment with platinum-based therapy and etoposide, and 9 had received topotecan. Responses are shown in the Table. Among reported adverse events so far (n=27), grade 3+ drug-related toxicities above 5% incidence are neutropenia (33%) and diarrhea (7%). No pt developed antibodies (by ELISA) to the antibody or drug. Conclusions: Encouraging objective responses with a good therapeutic index support further study of IMMU-132 in pts with previously treated mSCLC. Clinical trial information: NCT01631552.IMMU-132 Dosage Objective Response Rate (PR) including confirmed and unconfirmed data Clinical benefit (PR+ SD > 4 Months Median Progression-Free Survival (Months) (% Maturity) Median Overall Survival (Months) (% Maturity) 8 mg/kg (N=15) 15% 31% 2.0 (87%) 8.1 (60%) 10 mg/kg (N=13) 31% 54% 4.6 (77%) 8.3 (46%)