The pharmacokinetic results of this phase Ib study of ramucirumab combined with paclitaxel as second-line therapy in Japanese patients with metastatic gastric or gastro-esophageal junction adenocarcinoma are in line with previous ramucirumab studies.This combination at the doses and schedule given did not result in any dose-limiting toxicities and appeared to be safe and well tolerated.
This phase Ib study evaluated the tolerability and pharmacokinetics of ramucirumab, an anti-VEGFR-2 antibody, combined with paclitaxel as second-line therapy in Japanese patients with metastatic gastric or gastroesophageal junction adenocarcinoma after first-line therapy with fluoropyrimidines and/or platinum.
Patients received ramucirumab 8 mg/kg on days 1 and 15 and paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Safety analyses included all patients (n = 6).
No dose-limiting toxicities occurred in the first cycle. All patients experienced ≥1 treatment-emergent adverse event (TEAE); 5 patients experienced grade ≥3 TEAEs. There were two deaths caused by disease progression. The best overall responses were stable disease (n = 5) and partial response (n = 1). Patients received ramucirumab and paclitaxel for a median of 12.5 weeks (range: 11.4-42.7 weeks) and 12.2 weeks (range: 11.0-41.0 weeks), respectively. Following a single dose of ramucirumab IV infusion 8 mg/kg, clearance was ∼0.017 L/hour, half-life (t1/2) was 138 to 225 hours, and steady-state volume of distribution (Vss) was ∼3 L.
The ramucirumab/paclitaxel combination appears to be well-tolerated in Japanese patients with advanced gastric adenocarcinomas. These results are in line with previous ramucirumab pharmacokinetic studies as anticipated.
©AlphaMed Press; the data published online to support this summary is the property of the authors.

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On April 12, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that preclinical results from OncoSec’s collaboration with Heat Biologics, Inc. will be featured as a poster presentation at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held on April 16-20, 2016 in New Orleans, LA (Press release, OncoSec Medical, APR 12, 2016, View Source [SID:1234510706]).

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Details of the poster presentation are as follows:

Abstract Title: In vivo intra-tumoral electroporation of Gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens (Abstract ID #567)
Session Title: Immune Modulating Agents 1
Date and Time: April 17, 2016 at 1:00 p.m. – 5:00 p.m. CT
Location: Section 26

EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2-induced suppression of TNFα production in human whole blood. From this class, a potent and highly bioavailable compound (6) has been selected for potential clinical studies. EP4 binding and functional data, selectivity, and pharmacokinetic properties of this compound are included.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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On April 12, 2016 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that it will present three scientific posters at the American Association of Cancer Research meeting in New Orleans, Louisiana from April 16 – 20, 2016 (Press release, Rigel, APR 12, 2016, View Source;p=RssLanding&cat=news&id=2156237 [SID:1234510707]). The posters will provide data from the company’s preclinical research projects focused on the important oncology and immuno-oncology targets, IRAK, AMPK and MerTK. Rigel plans to partner select preclinical research programs in the future.

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An overview of each project and the corresponding AACR (Free AACR Whitepaper) presentation information follows:

IRAK
Rigel has an active IRAK preclinical research program aimed at understanding the role that certain inflammatory signals play in creating malignant changes in cells. IRAKs are key components in the signal transduction pathways associated with inflammation in humans. The company’s researchers have identified a family of IRAK4 inhibitors that are potent regulators of the inflammatory signal and are being evaluated for their potential utility in treating hematological cancers.

Abstract #: 346
Presentation Title: Potential role for R191, potent and selective IRAK4 kinase inhibitor, in treatment of hematological malignancies
Presentation Date: Sunday, April 17, 1:00pm – 5:00pm
Location: Section 17
Poster Board #: 2

AMPK
AMPK is a master regulator of cellular energy homeostasis and is an attractive research subject for its role in the metabolism of certain cancers, and other human diseases. Rigel has identified several potent direct AMPK activators, and is evaluating their potential to selectively activate AMPK within certain cancer cells to make them susceptible to the destructive properties of chemotherapeutic agents.

Abstract #: 3021
Presentation Title: Development of small molecule direct AMPK activators for the treatment of cancer
Presentation Time: Tuesday, April 19, 8:00am – 12:00pm
Location: Section 17
Poster Board #: 11

MerTK
Mer is a member of the TAM kinase family (Tyro3, AXL, Mer) known to provide tumor survival signals and support immunosuppressive tumor microenvironments. Rigel’s research on this family of receptor tyrosine kinases, also produced the AXL kinase inhibitor (R428/BGB324) currently in Phase 1 oncology studies with partner BerGenBio. The subject of the AACR (Free AACR Whitepaper) presentation is the company’s work with proprietary, orally delivered small molecules that block MerTK activity in vivo.

Abstract #: 4869
Presentation Title: Small molecule inhibitors of the anti-inflammatory TAM receptor MerTK
Presentation Time: Wednesday, April 20, 8:00am – 12:00pm
Location: Section 22
Poster Board #: 10

CD44v6, a member of the CD44 family of transmembrane glycoproteins is a co-receptor for two receptor tyrosine kinases (RTKs), Met and VEGFR-2 (vascular endothelial growth factor receptor 2). CD44v6 is not only required for the activation of these RTKs but also for signalling. In order to understand the role of CD44v6 in Met and VEGFR-2 activation and signalling we tested whether CD44v6 binds to their ligands, HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor), respectively. FACS analysis and cellular ELISA showed binding of HGF and VEGF only to cells expressing CD44v6. Direct binding of CD44v6 to HGF and VEGF was demonstrated in pull-down assays and the binding affinities were determined using MicroScale Thermophoresis, fluorescence correlation spectroscopy and fluorescence anisotropy. The binding affinity of CD44v6 to HGF is in the micromolar range in contrast with the high-affinity binding measured in the case of VEGF and CD44v6, which is in the nanomolar range. These data reveal a heparan sulfate-independent direct binding of CD44v6 to the ligands of Met and VEGFR-2 and suggest different roles of CD44v6 for these RTKs.
© 2015 Authors.

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