bluuebunny/crossref_metadata_2025_split huggingface dataset:
INDUCE-1: A phase I open-label study of GSK3359609, an ICOS agonist antibody, administered alone and in combination with pembrolizumab in patients with advanced solid tumors.
Authors: Angevin Eric , Barnette Mary S. , Bauer Todd Michael , Cho Daniel C. , Ellis Catherine Elizabeth , Gan Hui Kong , Hansen Aaron Richard , Hoos Axel , Jewell Roxanne C , Katz Jessica , Martin-Liberal Juan , Maio Michele , Mayes Patrick A. , Millward Michael , Moreno Victor , Olszanski Anthony J. , Rischin Danny , Schellens Jan H. M. , Yadavilli Sapna , Zhou Helen 
Published: September 2018

TPS3113 Background: Inducible T cell Co-Stimulator (ICOS), a member of the CD28/B7/CTLA-4 receptor superfamily expressed on T cells after engagement with cognate antigen and activation, provides a co-stimulatory signal augmenting T cell proliferation, survival and cytokine production. GSK3359609 is a humanized IgG4 antibody selected for its potent agonist activity against human ICOS. The unique mechanistic profile of an ICOS agonist antibody, such as GSK3359609, offers an opportunity to investigate the antitumor potential of targeting a T cell co-stimulator alone and in combination with other cancer immunotherapies such as pembrolizumab. Methods: INDUCE-1 is a first- in-human study evaluating safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of GSK3359609 administered as an intravenous (IV) infusion once every 3 weeks (Q3W) alone (Part 1) and in combination with 200 mg pembrolizumab (Q3W IV infusion) or other immunotherapy (Part 2) in approximately 304 adult patients. In dose escalation, eligible patients are required to have selected relapsed/refractory solid tumors. Primary objective is to determine safety, tolerability, and maximum tolerated or administered dose. Modified toxicity probability interval method will inform dose escalation decisions (minimum 3 patients per dose level [DL]). In expansion, cohorts may be defined by factors such as tumor histology, biomarker features, or prior treatment. More than one GSK3359609 DL may be evaluated in an expansion cohort by random assignment. Blood immunophenotyping is monitored in all patients; tumor biopsies (before and on-treatment) are optional in escalation and required in expansion to provide biomarker data that may inform on optimal dose selection as well as mechanistic understanding of GSK3359609. Efficacy measures are every 9 weeks and are according to immune-related RECIST. As of 7 Feb 2017, the first 3 monotherapy DL cohorts completed without dose limiting toxicities; DL 4 enrollment is ongoing. Study is funded by GlaxoSmithKline and is in collaboration with Merck & Co., Inc. Clinical trial information: NCT02723955.
Multicenter phase I/II trial of BBI608 and pembrolizumab combination in patients with metastatic colorectal cancer (SCOOP Study): EPOC1503.
Authors: Kuboki Yasutoshi , Kawazoe Akihito , Komatsu Yoshito , Nishina Tomohiro , Shinozaki Eiji , Hara Hiroki , Yuki Satoshi , Fukutani Miki , Tsukahara Natsuko , Hasegawa Hiromi , Hirano Nami , Nomura Shogo , Togashi Yosuke , Nishikawa Hiroyoshi , Sato Akihiro , Ohtsu Atsushi , Yoshino Takayuki 
Published: September 2018

TPS3623 Background: Immune checkpoint inhibitor (ICI) was reported to show durable responses in patients with MSI-H (Microsatellite Instability-High) metastatic colorectal cancer (mCRC). On the other hand, for patients with MSS (Microsatellite Stable) mCRC, ICI monotherapy achieved no response. Recently, WNT/β-catenin signaling has been reported to be involved in the elimination of tumor-infiltrating lymphocytes and the resistance of anti-PD-L1 antibodies. CRC is representative cancer with WNT/β-catenin pathway activation. Furthermore, STAT3 has also been reported to be a key driver of this immune evasion. Considering these rationales, the blocking of these signaling pathways with ICI may enhance antitumor immune response. Therefore, we initiated phase I/II study to assess efficacy and safety for the combination of BBI608, which blocks STAT3 and WNT/β-catenin signaling, with pembrolizumab in patients with mCRC. Methods: The eligibility criteria were patients with gastrointestinal cancer not responded to or intolerant of standard chemotherapies (SOC) for phase I part, and MSS mCRC refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, and anti-EGFR antibody (if wild-type RAS) for Cohort B in phase II part. For Cohort A, MSI-H mCRC refractory or intolerant to the SOC, irrespective of anti-EGFR antibody are investigated. Phase I part was designed to determine the recommended phase II dose in a “3+3” cohort-based dose escalation design of BBI608 (240mg BID every day on level 1 and 480mg BID every day on level 2) with pembrolizumab (200mg/body q3w). Primary endpoint of the phase II part is Immune-related objective response rate (irORR) determined by their Response Evaluation Criteria In Solid Tumors (irRECIST). A null hypothesis and alternative hypothesis for cohort B are irORR = 5% and 20%, respectively. Required sample size for Cohort B was 40 with a one-sided alpha of 5% and power of 90%. Required sample size for Cohort A (10 patients) was determined in an exploratory manner. We also investigate biomarker study using paired samples of both tumor biopsy and blood. The enrollment to phase I part began in November 2016. Clinical trial information: NCT02851004. Clinical trial information: NCT02851004.
A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of GS-5745 combined with mFOLFOX6 as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Authors: Bendell Johanna C. , Starodub Alexander , Huang Xi , Maltzman Julia D. , Wainberg Zev A. , Shah Manish A. 
Published: September 2018

TPS4139 Background: GS-5745 is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. Inhibiting MMP9 blocks paracrine signaling and metastasis and alters the tumor immune microenvironment. GS-5745 (800 mg q 2 weeks) with mFOLFOX6 was examined in a Phase 1b study in 40 patients with gastric and GEJ adenocarcinoma (GS-US-296-0101), and demonstrated encouraging activity without added toxicity (10% CR, median PFS 10.7 mo (Shah et al ASCO GI 2017, a108)). Decreased free MMP9 suggested inhibition of MMP9 enzymatic activity by GS-5745. These data support the hypothesis that GS-5745 treatment inhibits MMP9 activity and that the inhibition may lead to improved clinical outcomes. Methods: This phase 3, randomized, double-blind, multicenter study investigates the efficacy and safety of GS-5745 combined with mFOLFOX6 in subjects with untreated gastric and GEJ adenocarcinoma. Total of 430 eligible subjects with advanced gastric and GEJ cancer will be randomized in a 1:1 manner to mFOLFOX6 plus GS-5745 or mFOLFOX6 plus placebo. Stratification factors include ECOG status (0 v 1), geographic region (Latin America v All other countries), and primary tumor site (gastric v GEJ). CT or MRI scans will be performed every 8 weeks to evaluate response to treatment. mFOLFOX6 will be administered on Days 1 and 15 of each 28-day treatment cycle for a total of 6 cycles followed thereafter by leucovorin (LV) and 5-fluorouracil (5-FU) dosing on Days 1 and 15 of each 28-day treatment cycle until disease progression. GS-5745/placebo 800 mg will be infused on Days 1 and Day 15 of each 28 day cycle until disease progression. Primary endpoint is OS, and secondary endpoints include PFS, ORR (RECIST 1.1), and safety. The study is designed to have an 85% power to detect clinically meaningful improvement in overall survival at the one-sided significance level of 0.025. The association of exploratory biomarkers with study drug response will also be evaluated. Enrollment opened Oct. 2015. Clinical trial information: NCT02545504.
The “RENAISSANCE” Trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction—A phase III trial of the German AIO/CAO-V/CAOGI.
Authors: Mueller Daniel Wilhelm , Moenig Stefan Paul , Vogel Arndt , Lorenzen Sylvie , Homann Nils , Reissfelder Christoph , Bolling Claus , Blau Wolfgang , Schmiegel Wolff H. , Michl Patrick , Caca Karel , Schwarzbach Matthias , Hofheinz Ralf , Roedel Claus , Shah Manish A. , Sasako Mitsuru , Bechstein Wolf O. , Lang Hauke , Pauligk Claudia , Al-Batran Salah-Eddin 
Published: September 2018

TPS4140 Background: Recent data indicates that surgical resection may bring a benefit for select patients with metastatic gastric / esophagogastric junction cancer. However, no data obtained in randomized trials is available up to now. The current RENAISSANCE trial investigates this long-lasting question about the role of surgical intervention in limited-metastatic gastric / esophagogastric junction cancer. Methods: This is a prospective, multicenter, randomized, investigator initiated phase III trial. In this study, previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) will receive 4 cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2,600 mg/m²), and if Her2+ with trastuzumab. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will be randomized. The primary endpoint is overall survival; main secondary endpoints are quality of life parameters as assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 21 patients have been enrolled. EudraCT: 2014-002665-30. Clinical trial information: NCT02578368.
A multicohort phase II study of durvalumab plus tremelimumab for the treatment of patients (PTS) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) or lung origin (the DUNE trial-GETNE1601-).
Authors: Matos Garcia Ignacio , Grande Enrique , Garcia-Carbonero Rocio , Lopez Carlos , Teule Alexandre , Capdevila Jaume 
Published: September 2018

TPS4146 Background: NENs include a heterogeneous group of tumors with different behavior. Despite immunomodulators such as interferon are approved for the management of grade 1-2 NENs, the low mutation tumor load and PD-1/PDL-1 expression have limited the development of immune check-point inhibitors in this setting. The rational for immunotherapy in high grade NENs is stronger compared with low grade NENs based on the results observed in small cell lung cancer. However, the combination of an antiPDL-1 and antiCTLA-4 could increase the probability of success regardless of tumor growth rate, mutational tumor load or PDL-1 expression in low grade NENs. Methods: This prospective, multi-center, open label, phase II study (EudraCT:2016-002858-20) will evaluate the efficacy and safety of durvalumab plus tremelimumab in 126 pts within four different cohorts, including well-moderately differentiated lung NENs (Cohort 1), grade 1-2 gastrointestinal NENs (Cohort 2), grade 1-2 pancreatic NENs (Cohort 3) and grade 3 GEP NENs (Cohort 4). To optimize the efficacy of immunotherapy in low grade NENs, pts included in the trial must have progressed to all standard approved therapy in each setting, including somatostatin analogues, targeted agents and chemotherapy for lung and GEP grade 1-2 NENs up to 4 prior lines. For pts included in cohort 4, progression to standard platinum-based chemotherapy is mandatory. All pts will receive durvalumab 1500 mg every 28 days for 12 months, and tremelimumab 75 mg Q4W up to 4 doses/cycles. Retreatment is allowed after disease progression in the follow-up period. The primary endpoint of the study for cohorts 1-3 is disease control rate at 9 months including the percentage of pts achieving complete response, partial response, or stable disease according to RECIST v1.1; Median overall survival will be the primary endpoint for cohort 4. Primary endpoints will be assessed by investigators and confirmed by central radiological review. Secondary endpoints include median progression-free survival, safety and tolerability and a wide panel of biomarkers in blood samples and tumor tissue. Clinical trial information: 2016-002858-20.
The CCTG PA.7 trial: A randomized phase II study of gemcitabine and nab-paclitaxel vs. gemcitabine, nab-paclitaxel, durvalumab, and tremelimumab as 1st line therapy in metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Renouf Daniel John , Kavan Petr , Dhani Neesha C. , Jonker Derek J. , Wei Alice Chia-chi , Hsu Tina , Tang Patricia A. , Graham Barbara , Tu Dongsheng , O'Callaghan Christopher J. 
Published: September 2018

TPS4149 Background: Gemcitabine (GEM) and Nab-Paclitaxel (Nab-P) has become a standard 1st line therapy for advanced PDAC based on the MPACT Trial.Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor (PD-1). Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Monotherapy with immune checkpoint inhibitors has thus far demonstrated limited activity in PDAC. This may be partly related to the activity of cancer associated fibroblasts (CAF) in promoting an immunosuppressive tumoural microenvironment in PDAC. GEM and Nab-P treatment may deplete stroma and CAFs, release neo-antigens and increase the immunogenicity of PDAC. This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to GEM/Nab-P increases treatment efficacy. Methods: This randomized phase II study (ClinicalTrials.gov NCT02879318) will assess the efficacy and safety of GEM/Nab-P vs. GEM/Nab-P/D/T in patients (pts) with metastatic PDAC (n = 190). Good performance status pts (ECOG < 2) with untreated metastatic PDAC will be eligible. Prior adjuvant therapy is allowed provided recurrence is > 6 months post-completion. There is a safety lead in of 10 pts receiving GEM/Nab-P/D/T. Assuming no safety concerns the study will go on to randomize pts in a 2:1 ratio to receive GEM (1000mg/m2 D1, 8, 15)/Nab-P (125mg/m2 D1, 8, 15) with/without D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is overall survival; secondary endpoints include progression free survival, safety, overall response rate and quality of life. Analysis will be according to randomized group stratified by ECOG PS and receipt of prior adjuvant chemotherapy. Blood, plasma, and archival tissue will be collected and assessed for potential prognostic and predictive biomarkers. As of February 1 2017, 11 pts have been enrolled and the initial safety analysis is ongoing. Clinical trial information: NCT02879318.
A phase II study of abemaciclib as a monotherapy and in combination with other agents in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Chiorean E. Gabriela , Hochster Howard S. , Nanda Shivani , Thornton Donald , Klise Suzanne 
Published: September 2018

TPS4150 Background: PDAC is a lethal tumor with unusual resistance to cytotoxic and targeted therapies, and pathogenesis frequently associated with hyperactive CDK 4&6 signaling. Pre-clinical models have demonstrated anti-proliferative activity with CDK 4&6 inhibitors alone, however, synergistic effects have been observed when combined with a PI3K/mTOR or TGF- βR1 inhibitor. Abemaciclib is a selective inhibitor of CDK 4&6 with an acceptable safety profile in clinical studies.This study will evaluate the safety and efficacy of abemaciclib alone or in combination with LY3023414, a PI3K/mTOR dual inhibitor, or galunisertib, a TGF-βR1 inhibitor, versus standard of care (SOC) in pateints (pts) with metastatic PDAC. Methods: Design: Study JPCJ is an adaptive, open-label, randomized, Phase 2 study in pts with previously treated metastatic PDAC. Pts will be stratified based on number of prior systemic therapies (1 or 2), and in Stage 1 (25 pts/arm) will be randomized in a 1:1:1:1 ratio to 4 treatment arms: abemaciclib; abemaciclib+LY3023414; abemaciclib + galunisertib; SOC treatment gemcitabine or capecitabine. Investigational arms demonstrating evidence of disease control rate (DCR) comparable to or better than the SOC will advance to Stage 2 (additional 50 pts/arm). Eligibility: Pts must have metastatic PDAC with disease progression following 1 or 2 prior lines of therapy, measurable disease, ECOG PS ≤1, no prior treatment with any CDK 4&6, TGF-β, or PI3K and/or mTOR inhibitors, no severe cardiac disorders, and must not have insulin-dependent diabetes. Objectives: The primary endpoint is to evaluate the DCR (Stage 1) and progression-free survival (PFS [Stage 2]). Secondary objectives include response rate, overall survival, safety, pharmacokinetics, biomarkers related to the CDK 4&6 pathway, and quality of life. Statistics: Assuming a hazard ratio of 0.65 in PFS (median PFS of 2.3 months in abemaciclib containing arms vs. 1.5 months in the SOC arm), the study has approximately 76% power to detect superiority of the abemaciclib-containing arm using a 2-sided log-rank test at 0.10 significance level. Accrual began on 01/12/2017. Clinical trial information: NCT02981342.
SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX vs. gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinoma.
Authors: Sohal Davendra , McDonough Shannon L , Ahmad Syed A. , Gandhi Namita , Beg Muhammad Shaalan , Wang-Gillam Andrea , Guthrie Katherine , Lowy Andrew M. , Philip Philip Agop , Hochster Howard S. 
Published: September 2018

TPS4152 Background: Clinical outcomes after curative therapy for resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. Series show that 70-85% of patients die of systemic recurrence. Improved overall survival (OS) in the metastatic setting with the use of multi-agent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) holds the promise of progress in the curative setting as well. However, aggressive systemic therapy is usually not feasible after major pancreatic surgery. Therefore, early control of systemic disease by increased preoperative chemotherapy may improve outcomes. Furthermore, the perioperative platform facilitates early identification of patients with chemotherapy-resistant tumors and allows prospective biomarker studies in the future. Methods: This is a randomized phase II study intended to choose the most promising perioperative regimen to test in a larger trial. Eligibility requirements include adult patients with an ECOG PS of 0 or 1, a confirmed histopathologic diagnosis of PDA, and resectable disease as confirmed by central radiology review: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); no involvement, or < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Treatment includes 12 weeks [either 6 doses of mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin), or 9 doses of gemcitabine/nab-paclitaxel, on standard schedules] of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy. Primary outcome is 2-year OS, using a “pick the winner” design with minimum two-year OS of 40% assuming a 58% alternative hypothesis, 88% power, and a 1-sided α of 0.05, providing 90% probability of selecting the better regimen with a total sample size of 118 patients. Correlative studies are planned. The study opened through the National Clinical Trials Network (NCT02562716), and is supported by NIH/NCI/NCTN grants CA180888, CA180819, CA180821, CA180833. Clinical trial information: NCT02562716.
Phase 3 KEYNOTE-361 trial: Pembrolizumab (pembro) with or without chemotherapy versus chemotherapy alone in advanced urothelial cancer.
Authors: Powles Thomas , Gschwend Juergen E. , Loriot Yohann , Bellmunt Joaquim , Geczi Lajos , Vulsteke Christof , Abdelsalam Mahmoud , Gafanov Rustem , Bae Woo Kyun , Revesz Janos , Yamamoto Yoshiaki , Anido Urbano , Su Wen-Pin , Fleming Mark T. , Markus Maurice , Feng Dai , Poehlein Christian Heinrich , Alva Ajjai 
Published: September 2018

TPS4590 Background: Only 5%-15% of patients (pts) with advanced bladder cancer attain long-term survival with standard first-line cisplatin-based chemotherapy. Programmed death 1 (PD-1)/PD-L1 inhibitors have proven effective in recurrent, advanced urothelial cancer. Emerging data suggest these agents may also be useful in the first-line setting. In KEYNOTE-052, first-line pembro, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in cisplatin-ineligible pts with advanced urothelial cancer. KEYNOTE-361 (NCT02853305) is a randomized, open-label, phase 3 study of pembro with or without chemotherapy versus chemotherapy alone in pts with advanced urothelial carcinoma. Methods: Key eligibility criteria include age ≥18 years; histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra; measurable disease (RECIST v1.1, investigator review); no prior systemic chemotherapy ([neo]adjuvant platinum-based chemotherapy with recurrence > 12 months after completion is allowed); ECOG PS 0-2; and provision of a tumor sample for biomarker analyses. Pts will be randomly assigned 1:1:1 to receive pembro 200 mg every 3 weeks (Q3W), pembro + investigator’s choice of chemotherapy (gemcitabine [1000 mg/m2 on day 1 and 8 Q3W] + cisplatin [70 mg/m2 Q3W]), or chemotherapy alone. Cisplatin-ineligible pts randomly assigned to chemotherapy will receive gemcitabine + carboplatin [AUC 5 Q3W]. Chemotherapy choice must be selected before randomization. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or 35 cycles of pembro (pembro arms only). Response will be assessed Q9W for the first year and Q12W thereafter. AEs will be evaluated throughout and graded per NCI CTCAE v4.0. Primary end points are progression-free survival (RECIST v1.1 per central review) and overall survival; secondary end points include objective response rate and safety and tolerability. Efficacy outcomes will be compared for pembro vs chemotherapy and pembro + chemotherapy vs chemotherapy. Enrollment is ongoing; ~990 pts will be enrolled. Clinical trial information: NCT02853305.