bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase Ib/II study of onvansertib (PCM-075) in combination with FOLFIRI and bevacizumab for second-line treatment of metastatic colorectal cancer (mCRC) in patients with a KRAS mutation.
Authors: Lenz Heinz-Josef , Ahn Daniel H. , Ridinger Maya , Erlander Mark G. , Barzi Afsaneh 
Published: February 2020

TPS265 Background: FOLFOX (5-flourouracil, leucovorin, oxaliplatin) and FOLFIRI (fluorouracil, leucovorin, irinotecan) in combination with targeted agents are standard-of-care options for patients for mCRC with response rates >50% in first line. In the second line setting, efficacy of chemotherapy and targeted agents are much lower with response rates of 4% for FOLFIRI + bevacizumab and treatment options are limited in particular for the 50% of patients harboring a RAS mutation. Polo-like kinase 1 (PLK1) is a serine/threonine kinase, master regulator of G2/M cell-cycle progression and genome wide RNAi screens identified PLK1 to be synthetic lethal for KRAS mutated tumor cells inducing cell cycle arrest and apoptosis. Onvansertib is an oral, highly selective PLK1 inhibitor that demonstrated single agent activity and synergistic activity with irinotecan in preclinical CRC models. Additionally, KRAS mutated cells showed higher sensitivity to onvansertib than isogenic KRAS wild-type cells. PLK1 inhibition is a potential target in KRAS-mutated mCRC and onvansertib + FOLFIRI may provide a new second-line treatment option. Methods: The primary objective of this single-arm Phase 1b/2 study (NCT03829410) is to assess the safety and preliminary efficacy of onvansertib in combination with FOLFIRI and bevacizumab in the second line setting for KRAS-mutated mCRC patients. The phase 1b will determine the MTD or RP2D using a traditional 3+3 design, with onvansertib initial dose at 12 mg/m2. The phase 2 will enroll 26 patients at the RP2D to further assess the safety of the combination and to evaluate preliminary anti-tumor activity measured by objective response rate (ORR, RECIST v1.1). Based on a one-sided one sample log-rank test with 10% Type I error, there will be at least 90% power to detect an improvement in ORR from 5% to 20% with 26 patients. Exploratory studies include quantitation of KRAS circulating tumor DNA (ctDNA) and genomic studies of circulating tumor cells and ctDNA to determine altered pathways associated with patient response. Clinical trial information: NCT03829410.
Quattro-II study: A multicenter randomized phase II study comparing capoxiri plus bevacizumab with FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer as the first-line treatment.
Authors: Tsuji Akihito , Yoshino Takayuki , Yamanaka Takeharu , Bando Hideaki , Satake Hironaga , Yamazaki Kentaro , Taniguchi Hiroya , Oki Eiji , Kotaka Masahito , Oba Koji , Miyata Yoshinori , Muro Kei , Komatsu Yoshito , Baba Hideo , Kato Takeshi 
Published: February 2020

TPS267 Background: The first-line FOLFOXIRI with Bevacizumab (BEV) is highly effective and regarded as one of standard-of-care treatments in patients (pts) with metastatic colorectal cancer (mCRC) despite a high incidence of adverse events (AEs) such as neutropenia and diarrhea. The AXEPT, Asian Phase III study showed CAPIRI+BEV [Capecitabine (CAP: 1600 mg/m2), Irinotecan (IRI: 200 mg/m2) and BEV (7.5 mg/m2)] q3wk was non-inferior to FOLFIRI+BEV in pts with the second-line mCRC, with a lower incidence hematologic toxicity favoring CAPIRI+BEV over FOLFIRI+BEV. Based on these, a reduced dose of CAP and IRI regimen in combination with Oxaliplatin (OX) and BEV, CAPOXIRI+BEV may be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: QUATTRO-II is an open-label, multicenter, randomized phase II study. Key eligibility criteria are as follows; age ≥20 years, ECOG performance status (PS) 0-1 (≥71 years age: PS 0), adequate organ function, and UGT1A1 single-heterozygous (UGT1A1*1/*6 or *1/*28) or wild-type (*1/*1) genotype. Pts are randomized to either the recommended dose of CAPOXIRI+BEV or FOLFOXIRI+BEV (OX: 85 mg/m2, IRI: 165 mg/m2, l-leucovorin: 200 mg/m2, 5-FU: 3200 mg/m2), with the strata of RAS/ BRAF status, previous adjuvant OX, tumor sidedness, and UGT1A1 status. Induction triplet chemotherapy plus BEV treatments are administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The recommended dose of CAPOXIRI+BEV will be determined as a safety-lead-in before moving forward to the phase II main part. The primary endpoint is progression-free survival (PFS). The similarity of PFS between the two arms is evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls in between 0.80 and 1.25. Ensuring 70% probability that the observed HR will be “0.8<HR<1.25” under the assumption of the true HR of 1.0, a total of 100 patients will be needed with 3-year study period. Secondary endpoints included overall survival, overall response rate, safety, and patient-reported outcome (FACT/GOG-Ntx4). The enrollment started in October 2019. Clinical trial information: NCT04097444.
A phase Ib study of near infrared photoimmunotherapy (NIR-PIT) using ASP-1929 in combination with nivolumab and for patients with advanced gastric or esophageal cancer (GE-PIT study, EPOC1901).
Authors: Kadota Tomohiro , Kotani Daisuke , Yoda Yusuke , Fukutani Miki , Wakabayashi Masashi , Nomura Shogo , Fuse Nozomu , Sato Akihiro , Yano Tomonori , Shitara Kohei 
Published: February 2020

TPS457 Background: Near Infrared Photoimmunotherapy (NIR-PIT) is a newly developed, molecular targeted cancer therapy based on conjugating a near infrared silica-phthalocyanine dye to a monoclonal antibody, which result in necrotic cell death of targeted cancer cell immediately after exposure to near infrared light. Phase IIa trial of NIR-PIT with RM-1929 (anti-EGFR antibody cetuximab conjugated to IRDye 700DX) showed a 43% objective response rate (ORR) for recurrent head and neck squamous cell carcinoma (Cognetti DM, et al.ASCO 2019 abstr 6014). Meanwhile, PD-1 blockade reverses adaptive immune resistance, resulting in activation of tumor infiltrating lymphocyte after NIR-PIT in syngeneic mouse models (Nagaya T, et al. Cancer immunology research. 2019). The objective of this study is to investigate the safety and efficacy of the NIR-PIT using ASP-1929 (analogous to RM-1929) in combination with nivolumab for advanced gastric or esophageal cancer. Methods: The study is an open-label, single-arm, single-center, Phase Ib clinical trial. Eligible patients are with unresectable esophagogastric squamous cell carcinoma or EGFR positive adenocarcinoma after standard chemotherapy. Dose escalation cohort is designed to determine the recommended dose of laser irradiation energy density in a “3+3” design (50, 75, and 100 J/cm2). Nivolumab of 240 mg on Day 1 and ASP-1929 of 640 mg/m2 on Day 8 is administered, and laser irradiation is performed under endoscopy using the laser PIT unit on Day 9. In expansion cohort, approximately 20 patients will be enrolled. The primary endpoint is proportion of incidence of dose-limiting toxicity, and the secondary endpoints are proportion of incidence of adverse events, ORR, local complete response rate, progression-free survival (PFS), local PFS, overall survival, and proportion of incidence of device malfunction. We also investigate several biomarkers using pre- and post-treatment biopsied samples. First patient will be enrolled in December 2019. Clinical trial information: JapicCTI-194969.
A global phase II trial-in-progress with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.
Authors: Lee Jeeyun , Culm-Merdek Kerry , Rege Jessicca Martin , Pippas Andrew William , Bendell Johanna C. , Chau Ian 
Published: February 2020

TPS459 Background: The majority of gastric cancer (GC) patients fail to derive sufficient benefit from currently available therapies. Pembrolizumab received accelerated approval in 2017 as a third-line therapy in PD-L1 positive GC patients with an ORR of 13.3%. Further studies in second- and third-line GC patients showed comparable outcomes when pembrolizumab was combined with chemotherapy. Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors, including TIMS and TAMS. Data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. Methods: This phase 2, multicenter, open-label, single-arm global study is designed to assess the safety, tolerability and efficacy of the bavituximab-pembrolizumab combination in advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy. Patients must be treatment naïve for checkpoint inhibitors. The study, started in August 2019, consists of an initial 3+3 de-escalation safety cohort to confirm the expansion cohort dose. A total of 80 patients will be enrolled. Primary endpoints will assess antitumor activity of the treatment combination on objective response rate using RECIST1.1, safety and tolerability. Secondary endpoints will evaluate antitumor characteristics, pharmacokinetics, and immunogenicity. Exploratory objectives include the evaluation of a novel biomarker signature panel and its relationship to efficacy outcomes.
EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): An open-label randomized controlled phase II study.
Authors: Smyth Elizabeth Catherine , Knoedler Maren Kristina , Nilsson Magnus , Wagner Anna Dorothea , Moehler Markus H. , van Grieken Nicole C.T. , Giraut Anne , Mauer Murielle E. , Lordick Florian 
Published: February 2020

TPS467 Background: Gastroesophageal adenocarcinoma patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Immune checkpoint blockade with nivolumab and ipilimumab has demonstrated activity in advanced gastroesophageal adenocarcinoma. We hypothesise that high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. The trial will recruit 240 patients at 24 number of sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Portugal, Spain, and United Kingdom. Recruitment commenced July 2019 and is anticipated to take 30 months. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.
Sgnlva-005: Open-label, phase II study of ladiratuzumab vedotin (LV) for advanced aerodigestive tract malignancies.
Authors: Anderson Ian Churchill , Wang Yinghui , Wang Zejing , Sanborn Rachel E. 
Published: February 2020

TPS469 Background: LIV-1 is a transmembrane protein with putative zinc transporter and metalloproteinase activity. It has been linked to the epidermal-to-mesenchymal transition that leads to malignant progression and metastasis. Ladiratuzumab vedotin (LV), also known as SGN-LIV1A, is an investigational antibody-drug conjugate (ADC) targeting LIV-1 that is composed of a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. MMAE-linked ADCs can induce mitotic arrest and immunogenic cell death. In a phase 1 study, LV was well tolerated and showed antitumor activity in heavily pretreated patients (pts) with metastatic breast cancer (Modi et al 2017). The current study was initiated to evaluate LV in previously treated pts with advanced upper aerodigestive tract malignancies. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy (2.5 mg/kg IV every 3 weeks) for pts with the following advanced malignancies: gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer (NSCLC)-squamous, NSCLC-nonsquamous, and head and neck squamous cell carcinoma. Up to approximately 30 pts with unresectable locally advanced or metastatic disease, measurable disease per RECIST v1.1, an ECOG score of 0 or 1, and adequate organ function are enrolling in each of the cohorts. Pts in the gastric and GEJ adenocarcinoma and esophageal squamous cell carcinoma cohorts must have received no more than 1 prior line of platinum-based cytotoxic chemotherapy and pts in the gastric and GEJ adenocarcinoma cohort should have received prior anti-PD(L)1 therapy if indicated. The study consists of a 2-stage design that includes a Bayesian predictive probability of success approach to determine futility criteria. Study objectives include objective response rate (primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study enrollment is ongoing in North America. Pts will also enroll in Europe and Asia. Clinical trial information: NCT04032704.
A multicenter phase II trial of tumor treating fields plus chemotherapy for first-line treatment of gastric adenocarcinoma.
Authors: Li Jin , Yeo Winnie , Lam Ka-On 
Published: February 2020

TPS474 Background: Gastric carcinoma (GC) is the third-leading cause of death in China (291,000 deaths in 2015). Current therapies include surgery, chemotherapy, radiotherapy and targeted therapy, which prolong PFS and OS to 6 months and 8-14 months, respectively. Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality approved by the FDA for glioblastoma and malignant pleural mesothelioma. TTFields at specific frequency (100- 500 kHz) are delivered via transducer arrays placed on the skin of the upper abdomen, back, right and left hypochondriac regions where the primary tumor lesion is located. TTFields were effective in preclinical models of gastric cancer and there are several ongoing Phase 3 trials of TTFields in multiple solid tumors. In this phase 2, single arm, open-label, multi-center study, we will investigate for the first time the efficacy and safety of TTFields concomitant with XELOX (oxaliplatin/capecitabine) as the first-line treatment of GC. Methods: Patients (N = 50) with histologically confirmed unresectable, locally advanced or metastatic Gastroesophageal Junction (GEJ) or Gastric Adenocarcinoma (GC), aged ≥ 18 years, ECOG PS 0-1, who had no previous systemic treatment for the recurrent or metastatic disease will be enrolled. Patients will receive TTFields (150 kHz via the NovoTTF-100L (P) medical device for average monthly use of 18 hrs/day) plus XELOX chemotherapy (Oxaliplatin: 130 mg/m2 on day 1 every 3 weeks; Capecitabine: 1000 mg/m2, PO, BID on day 1-14 every 3 weeks). For HER-2 positive patients, trastuzumab is allowed. The primary endpoint is investigator-assessed Objective Response Rate (ORR) per RECIST 1.1. Secondary endpoints are time to tumor progression (TTP), progression-free survival (PFS), overall survival (OS), and 12-month OS rate. Adverse events (AEs) will be graded for severity according to CTCAE 5.0. Based on the historical ORR data in first-line chemotherapy in GC, we assumed that ORR will be higher than 45% with TTFields concomitant with chemotherapy. At least 45 patients need to be enrolled to ensure the lower boundary is 30% of the 95% CI. Estimating a patient drop-out rate of 10%, 50 patients will be actually enrolled.
Phase II trial of trifluridine/tipiracil and irinotecan for the treatment of advanced refractory biliary tract cancer.
Authors: Xie Hao , Borad Mitesh J. , Ahn Daniel H. , Bekaii-Saab Tanios S. , Tran Nguyen H. , Jin Zhaohui , Pitot Henry C. , Huebner Lucas J. , Shi Qian , Wessling Jaclynn , Durgin Lori M. , Liu Minetta C. , Hogenson Tara L. , Phillips William J , Fernandez-Zapico Martin , Alberts Steven R , Mahipal Amit 
Published: February 2020

TPS594 Background: Effective treatment options are very limited for patients with advanced refractory biliary tract cancer (BTC). Fluoropyrimidine-based chemotherapy regimen such as 5-fluorouracil and irinotecan are frequently utilized for these patients after first-line therapy despite lack of FDA approval. Trifluridine/tipiracil (FTD/TPI) is a novel oral nucleoside with antitumor activity in both fluoropyrimidine sensitive and resistant tumors due to its unique mechanisms of action. Given early toxicity and efficacy data from our previous study on single-agent trifluridine/tipiracil (FTD/TPI) in advanced BTC, the clinical evaluation of its combination with irinotecan represents a rational approach for the treatment of advanced refractory BTC. Methods: This is a single-arm phase II trial with a two-stage design to assess the efficacy of trifluridine/tipiracil (FTD/TPI) and irinotecan in advanced refractory BTC. Key eligibility criteria include histologically confirmed advanced, unresectable BTC who have progressed on at least one line of systemic therapy and have measurable disease per RECIST v1.1. Target accrual is 25. Treatment includes trifluridine/tipiracil (FTD/TPI) 25 mg/m2 on days 1-5 and irinotecan 180 mg/m2 on day 1 in 14-day cycles. Patients will be evaluated for response every 4 cycles and in the absence of disease progression, therapy may be given up to 2 years. The primary end point is the progression-free survival rate at 16 weeks. Secondary endpoints include overall response rate, disease control rate, progression-free survival, overall survival, and incidence of adverse events. Correlative biomarker studies include evaluations of circulating tumor DNA and circulating tumor cells at baseline, after 4 cycles and at progression; and development of patient-derived tumor organoids from pre-treatment biopsies for parallel treatments. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc. Clinical trial information: NCT 04072445.
A phase II randomized placebo-controlled study investigating the combination of yiv-906 and sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma (HCC).
Authors: Harding James J. , Abou-Alfa Ghassan K. , Shi Yuankai , Whang-Peng Jacqueline , Yuen Man Fung , Saif Wasif M. , Tian Aiping , Gu Shanzhi , Lam Wing , Liu Shwu-Huey , Cheng Yung-Chi , Chu Edward , Yen Yun 
Published: February 2020

TPS601 Background: First-line systemic treatment options for advanced HCC pts are limited to the multi-targeted tyrosine kinase inhibitors, SORA and lenvatinib. Both agents improve outcomes for pts with advanced disease, but are associated with increased rate of grade ≥ 3 treatment-related adverse events. YIV-906 (PHY906, KD018) is derived from Huang-Qin-Tang, a traditional Chinese medicine documented 1800 years ago to treat gastrointestinal ailments. Preclinical data indicate YIV-906 increases inflammation in the tumor microenvironment by M1 macrophages activation/proliferation resulting in HCC tumor rejection in vivo and reduces SORA associated toxicity. Clinical experience with YIV-906 plus SORA suggests safety and potential clinical benefit to HCC pts with chronic HBV infection. Methods: This is a proof-of-concept, international, multicenter, double-blind, placebo-controlled, randomized phase 2 study designed to compare the efficacy of YIV-906 and SORA to SORA alone in advanced HCC pts (NCT04000737). Key eligibility criteria include age ≥ 18 years, HBV-associated HCC, ≥ 1 measurable untreated lesion, Child-Pugh A liver function, and no prior systemic therapy. An estimated 125 pts will be randomized 2:1 to receive the investigational (YIV-906 plus SORA) or control (placebo plus SORA) arm until disease progression or unacceptable toxicity. Pts will be stratified by metastatic status (extrahepatic/vascular invasion vs none) and ECOG performance status (0 vs. 1). The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate and disease control rate by mRECIST, time to progression, overall survival, quality of life, and safety by CTCAE version 4.0. Translational correlatives include pharmacokinetics, effects on oral/gut microbiota, and exploratory soluble biomarkers analysis. For the primary endpoint, sample size of 41 pts in control arm and 84 pts in the investigational arm achieves 90% power at a 0.05% significance level to detect a hazard ratio of 0.5 assuming the median PFS of the control SORA arm is 3.6 months and that of the combination arm is 7.3 months. Clinical trial information: NCT04000737.