bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter, open label, first-in-human study of an oncolytic viral vector expressing an agonistic anti-CD40 antibody (NG-350A) in patients with epithelial tumors (FORTITUDE).
Authors: Naing Aung , Ileana Dumbrava Ecaterina Elena , Murthy Ravi , Meric-Bernstam Funda , Fox Andrew , Krige David , Carter Jo , Champion Brian , Cockle Paul , Koetz Barbara , McElwaine-Johnn Hilary 
Published: May 2019

TPS2668 Background: NG-350A is a transgene modified variant of the oncolytic platform virus enadenotucirev (EnAd) which expresses a fully human agonist anti-cluster of differentiation 40 (anti-CD40) antibody. The principal advantage of encoding anti-CD40 within an oncolytic virus is the ability to potentially achieve very high levels within the tumor coupled with direct cytotoxicity due to viral lysis and stimulation of the immune-system. NG-350A infects and selectively replicates in tumor cells. The anti-CD40 antibodies are expected to activate the patient’s own dendritic cells, macrophages and B-cells to drive CD4+ and CD8+ T-cell immuno-inflammatory responses and immune mediated tumor cell killing. EnAd is a tumor-selective chimeric Ad11/Ad3 group B oncolytic adenovirus developed using directed evolution. Phase I clinical studies have identified a well-tolerated systemic dose and regimen for EnAd monotherapy. EnAd shows a high level of selective replication and cell killing for a broad range of carcinoma cell lines (of epithelial origin) with little replication in normal and non-carcinoma cells. Methods: This first in human study will evaluate the safety, tolerability and preliminary efficacy of NG-350A together with virus kinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A in patients with advanced or metastatic epithelial tumours. In the dose escalation phase up to 33 patients evaluable for dose-limiting toxicity will receive NG-350A by IV infusion on Day 1, 3 and 5 at 6 US sites. The first IV cohort in the dose-escalation phase will utilize the conventional ‘3+3’ design; thereafter dose recommendations will be based on a continual reassessment method. Following determination of the recommended phase 2 dose up to 20 patients will be treated in a dose-expansion cohort. In a parallel cohort, up to 12 patients will receive a single dose of NG-350A by intratumoural (IT) injection on Day 1 for direct delivery of high viral titres to tumor. Up to six patients are planned to undergo surgical resection of a tumor lesion to optimize translational research. Clinical conduct of the study was initiated in February 2019.
A phase II study for prostate cancer monitoring using 18F-DCFPyL and blood-based biomarkers.
Authors: Lim Emerson A. , Mintz Akiva , Stein Mark N. , Rai Alex J. , Mansukhani Mahesh M. , Aggen David Henry , Dallos Matthew , Hawley Jessica , Shaish Hiram A , Schwartz Lawrence Howard , Drake Charles G. 
Published: May 2019

TPS3154 Background: Assessing treatment response in castrate resistant prostate cancer (CRPC), remains a challenge due to the limited sensitivity and specificity of existing imaging modalities. Understanding prostate cancer biology with tumor biopsies does not address the issue of tumor heterogeneity or cellular degradation during the decalcification process of bone biopsies. Next generation positron emission tomography (PET) imaging and circulating biomarkers might provide additional insights on treatment responses and inform clinical decision-making earlier in therapy. 18F-DCFPyL (PyL) is a second-generation fluorinated PSMA PET tracer that has superior sensitivity and specificity to detect prostate cancer compared to standard imaging. Its role in assessing tumor response to therapy has not been evaluated. Circulating tumor DNA (ctDNA) in blood can provide tumor genomic information, while exosomes in serum and urine may provide data on the proteomic landscape of tumors. Methods: We are conducting a prospective study of 15 men with metastatic CRPC who are scheduled to start a new systemic therapy for their disease. Upon enrollment, subjects will have baseline assessments with standard cross-sectional imaging, 99mTc bone scan, and blood work. Standard scans will be performed every 8-12 weeks until progression of disease. PyL PET/CT scans and liquid biopsies (ctDNA and exosomes) will occur at baseline, 6 weeks after starting their new therapy, and at disease progression. Lesions seen on PET/CT images will be identified by a certified reader. The maximum standardized uptake value (SUVmax) will be measured and recorded in up to the five hottest lesions and normalized to a background SUVmean measured in the liver, spleen, kidney, mediastinum, and parotid glands. Changes in the normalized SUV from baseline to the 6-week PyL PET scan will be correlated to PSA response by the Pearson’s correlation coefficient. The Kaplan-Meier method will be used to evaluate progression free survival and overall survival dichotomized by the median value of SUV change. Blood for ctDNA and exosomes will be stored for future analysis. The study is open with two patients enrolled at the time of submission. One patient has completed his initial PyL PET/CT scan. Clinical trial information: NCT03585114.
Clinical Trial in Progress: The FLEX Big Data Platform explores new gene expression profiles and investigator-initiated protocols in early-stage breast cancer.
Authors: Untch Sarah , Srkalovic Gordan , Brufsky Adam , Crozier Jennifer A. , Habibi Mehran , Whitworth Pat W. , Cox Charles E. , D'Abreo Nina , Audeh William , Yoder Erin , Grady Ian 
Published: May 2019

TPS3155 Background: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer. To precisely stratify breast cancers into actionable subgroups, full genome expression data and matching clinical data must be aggregated into a large data set. Such a data set will accelerate research and discovery, especially for smaller patient subsets who are not as widely represented within the current body of literature. Methods: FLEX is a multicenter, prospective, population-based, observational trial for patients with Stage I, II, and III breast cancer. All patients with stage I to III breast cancer who receive MammaPrint, with or without BluePrint on a primary breast tumor are eligible for enrollment. The study’s primary aim is to create a large scale, population-based registry of full genome expression data matched with clinical data to investigate new gene associations with prognostic and/or predictive value. Secondary objectives include utilizing the shared study infrastructure to examine and generate hypotheses for targeted subset analyses and/or trials based on full genome expression data. The design of FLEX allows targeted sub-studies and sub-analyses to be added as appendices after the initial baseline study is opened. Patients enrolled in the initial study are also eligible for inclusion in sub-studies where they meet all criteria and additional consent is not required. Additional clinical data will be collected as specified in the appendix protocols. The FLEX collaborative platform allows participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee of their peers. 13 sub-studies have already been identified and are under development. Eligibility: The study will enroll a minimum of 10000 patients aged ≥18 years with histologically proven invasive stage I-III breast cancer who signed informed consent. Enrollment began April 2017 and 1506 patients have been enrolled. Clinical trial information: NCT03053193.
A window of opportunity trial of atorvastatin in p53-mutant and p53 wild type malignancies.
Authors: Telfah Mohammad , Iwakuma Tomoo , Bur Andres , Shnayder Lisa , Tsue Terry , Mazin Al-Kasspooles Mazin , Ashcraft John , Martin Benjamin , Al-Rajabi Raed Moh'd Taiseer , Kasi Anup , Khan Qamar J. , Lin Tara L. , Saeed Anwaar , Williamson Stephen K. , Chalise Prabhakar , Godwin Andrew K. , Reed Greg , Thomas Sufi , Komiya Takefumi , Baranda Joaquina Celebre 
Published: May 2019

TPS3165 Background: Mutations in p53 contribute to tumor progression. A rational approach is to destabilize mutant (m) p53. The group at the University of Kansas Cancer Center screened compounds that suppress m p53 in a preclinical model. Luciferase-based reporter assay identified statins as suppressors of m p53 expression. In vitro validation assay demonstrated atorvastatin (A) suppressed m p53 level and cell growth selectively; and depletion of mevalonic acid lead to degradation of m p53. These effects were limited to mutations in the conformation of p53, while wild-type and DNA contact mutations were not as sensitive to statin-induced degradation of p53. M p53 xenograft model confirmed that A could suppress tumor growth at a concentration that can decrease LDL level. The primary objective of this trial is to determine if A decreases the level of conformational m p53. The secondary objective is to assess the effects of A on Ki-67 and caspase-3 in conformational m p53 tumors. Methods: This is an open-label, window of opportunity pilot trial to see if A given for 1 to 4 weeks at a dose of 80 mg/day is sufficient to reduce the levels of conformational m p53 in the tumor tissues. Subjects with new diagnosis of malignancy with a planned surgical therapy, and subjects with previously treated AML, in between treatment regimens, are eligible. Tissues from solid tumors, and bone marrow or peripheral blood samples from AML will be used to screen for m p53 by immunohistochemistry (IHC). Subjects will receive A at 80 mg/day po for 1 to 4 weeks. Pharmacokinetics at pre-dose and 1-hour post-dose on Day 1 and on the day of surgery will be done. Mutational analysis using exome sequencing technique will be done on m p53. Using IHC, the amount of p53 in pre-treatment and post-treatment samples will be measured and compared simultaneously. The levels of Ki67 and caspace-3 will be tested and compared between pre-treatment and post-treatment samples in subjects with conformational m p53, between conformational and non-conformational m p53, and in wild-type p53 tumors. The trial is actively enrolling subjects. The results of this trial will determine further investigations on the role of atorvastatin in tumors with p53 mutations in a placebo-controlled, randomized trial. Clinical trial information: NCT03560882.
Leeomic: A comprehensive proteomic analysis towards discovery of predictive patterns of protein expression to ribociclib sensitivity and resistance—A compLEEment-1 Canadian correlative sub-study.
Authors: Chia Stephen K. L. , Henning Jan-Willem , Warner Ellen , Song Xinni , Joy Anil A. , Califaretti Nadia , Desbiens Christine , Zarate Juan Pablo , Haftchenary Sina , Perri Sabrina R. , Morin Gregg B. 
Published: May 2019

TPS3170 Background: Despite developments in the treatment of advanced hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, primary or acquired resistance eventually occurs in all cases and there is still very limited understanding of the mechanisms of resistance to therapy. LEEOMIC is a sub-study of the main CompLEEment-1 ( N = 3255 patients enrolled, CLEE011A2404 v03) trial, an open-label, phase 3b study evaluating ribociclib + letrozole as first-line therapy in an expanded advanced breast cancer patient population which recruited over 250 Canadian patients. The purpose of this Canadian correlative sample collection study is to explore the mechanisms of response and resistance to ribociclib in combination with letrozole through proteomic and ctDNA analysis. Methods: The British Columbia Cancer Research Centre team developed a novel and optimized MS/MS platform called SP3-Clinical Tissue Proteomics (SP3-CTP) to perform in-depth proteome profiling ( > 8,000 proteins) from formalin fixed paraffin embedded (FFPE) material (10-micron section). SP3-CTP analysis of the proteome of the study patients who did not achieve clinical benefit (primary resistance: progression within 3 months of treatment) will be compared to the proteome of the sub-group of prolonged responders (time to progression of 22 months or more) in order to identify biomarkers that can predict response or de-novo resistance to therapy. Archival tumor biopsies (primary or metastatic) collected from the study will be submitted for proteomic analysis to identify proteomic expression levels that may serve as predictor of response. It is anticipated that over 150 samples will be collected. If available, blood samples taken at time of progression or end of treatment will also be analyzed for ctDNA for genetic profiling and to study if there is any correlation between genetic mutations and response or resistance to therapy. Currently, both tissue and blood samples are being collected and no analysis has been conducted thus far. Clinical trial information: NCT03613220.
TENERGY: Multicenter phase II study of atezolizumab monotherapy following definitive chemoradiotherapy with 5-FU plus cisplatin in patients with locally advanced esophageal squamous cell carcinoma.
Authors: Bando Hideaki , Kotani Daisuke , Tsushima Takahiro , Hara Hiroki , Kadowaki Shigenori , Kato Ken , Chin Keisho , Yamaguchi Kensei , Kageyama Shun-ichiro , Hojo Hidehiro , Wakabayashi Masashi , Fukutani Miki , Togashi Yosuke , Fuse Nozomu , Nishikawa Hiroyoshi , Kojima Takashi 
Published: May 2019

TPS4141 Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are only 11% to 25%, and median overall survival (OS) is 9 to 10 months. The improved therapeutic efficacy of combining immunotherapy with radiation has been gaining interest. Our basic research suggested that sequential treatment with anti-PD-L1 agents soon after completion of CRT is the best combination. Twelve months of anti-PD-L1 antibody following platinum-based CRT significantly improved progression-free survival (PFS) and OS in patients with locally advanced non-small cell lung cancer (Antonia SJ, et al. N Engl J Med. 2018). Based on this background information, we have planned a phase II clinical trial to evaluate the safety and efficacy of atezolizumab monotherapy following definitive CRT in patients with locally advanced ESCC. Methods: The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of treatment with 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1–4, every 28 days), and adequate organ function. Within 4 weeks after CRT, patients will be registered in the study and started on 1200 mg of atezolizumab every three weeks until 12 months or disease progression. The primary endpoint is the CR rate by the investigator’s assessment. Overall response rate, PFS, OS, treatment-related adverse events, and CR rate by central assessment are secondary endpoints. A total of 50 patients will be enrolled, including 40 with primary locally advanced ESCC and 10 with postoperative loco regionally recurrent ESCC. As an exploratory biomarker study, biopsies from the primary site and blood collections will be performed at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab). We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutation burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. Clinical trial information: UMIN000034373.
Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Authors: Al-Batran Salah-Eddin , Pauligk Claudia , Hofheinz Ralf , Lorenzen Sylvie , Wicki Andreas , Siebenhuener Alexander Rheinhard , Schenk Michael , Welslau Manfred , Heuer Vera , Goekkurt Eray , Schmalenberg Harald , Thuss-Patience Peter C. , Waberer Lisa , Talbot Jonathan , Goetze Thorsten Oliver , Homann Nils 
Published: May 2019

TPS4142 Background: Perioperative FLOT chemotherapy has become a standard of care for locally advanced, resectable gastric cancer and adenocarcinoma of the GEJ. However, patient outcomes are still unsatisfactory and 5-year survival in T3-4 or nodal positive disease is still around 50%. Targeting the PD-1/PD-L1 pathway has proven active in different cancers, including esophagogastric cancer, and was associated with response rates in the 10-15% range in unselected, heavily pre-treated gastric cancer patients. Atezolizumab is a PD-L1 inhibitor with established efficacy and tolerability profiles. This study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with FLOT. Methods: This is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Eligibility status is centrally evaluated. Patients are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m²) followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS) as assessed by the Kaplan-Meier-Method. The statistical design is based on a target HR of 0.68, a power of 0.8, and a significance level of p< 0.05 (1-sided log rank test). A total of 295 patients will be randomized. Main secondary endpoints are rates of centrally assessed pathological regression (rates of complete and nearly complete pathological regression), overall survival, R0 resection, and safety. Recruitment started in Sept 2018; by February 2019, a total of 27 patients have been randomized. Clinical trial information: NCT03421288.
Phase II study of a telomerase-specific oncolytic adenovirus (OBP-301, Telomelysin) in combination with pembrolizumab in gastric and gastroesophageal junction adenocarcinoma.
Authors: Khan Uqba , Biran Talia , Ocean Allyson J. , Popa Elizabeta C. , Ruggiero Joseph T. , Paul Doru , Garcia Chelsea , Carr-Locke David , Sharaiha Reem , Urata Yasuo , Shah Manish A. 
Published: May 2019

TPS4145 Background: Although checkpoint inhibitors (CPIs) can produce durable responses in gastric cancer patients (pts) in the 3rd line setting, the response rate is only 10-15%. Therefore, there is a huge unmet need to enhance the response rate of CPIs to provide benefit to wide range of pts. A novel concept in immuno-oncology is the use of cancer specific oncolytic viral therapy. In addition to the specific killing of the tumor by the virus, these agents can induce an immunogenic cell death in the tumor to augment the immune activation driven by PD-1 inhibition. OBP-301 is an oncolytic adenovirus genetically modified to be able to selectively replicate in cancer cells by introducing human telomerase reverse transcriptase (hTERT) promoter. Results of a phase I study of OBP-301 in solid tumor pts demonstrated the safety and efficacy of intra-tumoral injection of OBP-301. A pre-clinical study of the combination of OBP-301 with anti-PD-1 antibody has also shown significant synergistic activity as well. Based on these encouraging pre-clinical and clinical data, we designed a phase II clinical trial to examine the safety and efficacy of combination of pembrolizumab and OBP-301 in the treatment of PD-L1 positive metastatic gastric/GEJ adenocarcinoma. Methods: This is a multicenter, non-randomized phase II trial of OBP-301 with pembrolizumab in metastatic gastric/GEJ adenocarcinoma that has progressed on at least 2 lines of prior therapy. Eligibility criteria include PD-L1 positive tumors as defined by a combined positive score, performance status ≤1, and good end organ function. The primary endpoints are to examine objective response rate and safety of OBP-301 with pembrolizumab. The secondary endpoints are to examine disease control rate, duration of response, overall survival and progression free survival. Correlative studies are planned to identify biomarkers for response to combination therapy by using multiparameter flowcytometry, single-cell transcriptional profiling and immunohistochemistry. All eligible pts will receive 1x1012Viral Particles/mL of OBP-301 administered every 2 weeks for total of 4 injections, injected directly into tumor via upper endoscopy. Every pt will also receive pembrolizumab 200 mg IV every 3 weeks for 2 years or until progression. Pts will be enrolled in a Simon two stage design, with 18 pts in the first stage. If 3 or more pts respond to the combination therapy, the study will move forward to stage 2, with 19 more pts enrolled. The study is currently enrolling pts.
A single-arm, open phase II clinical trial of anti-programmed death-1 antibody SHR-1210 combined with nimotuzumab as second-line treatment of advanced esophageal squamous cell carcinoma.
Authors: Wang Feng , Meng Xiangrui , Fan Qingxia 
Published: May 2019

TPS4147 Background: Approximately 40% of patients (pts) with esophageal cancer are diagnosed with advanced unresectable or metastatic disease; the 5-year survival rate for advanced disease is 5%. No standard therapy is available in China for Advanced Esophageal Squamous Cell Carcinoma(ESCC) patients progressed after first-line chemotherapy.Inhibition of programmed cell death protein-1 (PD-1) has demonstrated promising antitumor activity and manageable safety in pts with advanced unresectable or metastatic ESCC. SHR-1210, a humanized IgG4 monoclonal antibody, has high affinity and specificity for PD-1 molecule. SHR-1210 was generally well tolerated and had preliminary antitumor effects in pts with solid tumors, including ESCC. Nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody h-R3, has been shown to be effective and safe in the treatment of head and neck cancer,non-small cell lung cancer (NSCLC) and esophageal Cancer in several phase II studies.The purpose of this study is to observe and evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced ESCC. Methods: Patients, age 18-75, with measurable tumor lesion, failed in or progression after 1st line chemotherapy, were enrolled in this study.Patients received SHR-1210 200 mg once every 2 weeks (Q2W) combined nimotuzumab 200 mg weekly until disease progression, death or unacceptable toxicity.Assessments included response by RECIST v1.1 every 6 wks and safety (physical examination, vital signs, ECOG PS, laboratory tests).The primary endpoint is the objective response rate (ORR),and the secondary end points include the diseases control rate (DCR),duration of response (DOR),progression-free survival (PFS),and overall survival(OS). Additionally, we try to identify biomarker to predict efficacy of SHR-1210 and Nimotuzumab with target capture sequencing and gene expression profile as exploratory endpoints. Clinical trial information: NCT03766178.