e15749 Background: Ventana Medical Systems, Inc. is developing in collaboration with Halozyme Therapeutics an affinity histochemical companion diagnostic to aid in selecting patients with pancreatic ductal adenocarcinoma (PDA) that may benefit from PEGPH20 based therapy. Methods: A recombinant hyaluronan (HA) binding probe was optimized for use with the VENTANA OptiView DAB IHC Detection Kit on the automated BenchMark ULTRA platform (HA CDx Assay). HA is a non-sulfated glycosaminoglycan polymer that often accumulates in extra-cellular tumor matrices. The HA CDx Assay was developed for use in formalin-fixed, paraffin-embedded tissue samples of PDA in a series of studies addressing sensitivity, specificity, robustness, and precision. PEGPH20 is a pegylated form of recombinant human PH20 hyaluronidase degrading tumor-associated HA with high affinity and selectivity. The scoring algorithm was defined using statistical analysis of clinical outcome data and HA CDx Assay staining pattern observed in a set of HALO109-202 Phase 2 clinical trials samples. Inter-reader precision was established by 3 pathologists evaluating 100 PDA samples across the range of HA expression levels. Results: The Ventana HA CDx Assay met all pre-defined acceptance criteria. PDA are considered HA-high when the HA CDx Assay staining in the tumor extra cellular matrix (ECM) is ≥ 50% of the tumor surface. Inter-reader precision in determining HA status resulted in agreement rates greater than 94%. Conclusions: These results highlight the robustness and reproducibility of the Ventana HA CDx Assay. In HALO 109-202, patients identified by the Ventana HA CDx Assay algorithm as HA high demonstrated clinically meaningful improvements when treated with nab-paclitaxel and gemcitabine (AG) + PEGPH20 compared to those treated with AG alone. The clinical utility of the HA CDx assay will be further validated in additional patients in subsequent PEGPH20 studies, including a planned Phase 3 study beginning in 2016.
<p>Supplementary Tables 1-3. Supplementary Table 1. Use of cobas-like partial HPV typing in triage of ASC-US. Supplementary Table 2. Use of cobas-like partial HPV typing in co-testing. Supplementary Table 3. Use of cobas-like partial HPV typing in primary HPV testing</p>
4008 Background: Hyaluronan (HA) accumulation in the tumor microenvironment produces elevated tumor pressure, vascular compression, and reduced drug delivery. PEGPH20 degrades HA, increasing the access and therapeutic index of anticancer agents. Methods: In Stage 1 of this phase II study, pts with untreated mPDA were randomized 1:1 to PAG (P; 3 µg/kg IV 2x/wk x 3 wks in C1, then 1x/wk x 3 wks in C2+, plus AG) vs AG every 28 days. An imbalance in thromboembolic (TE) events in the PAG arm led to a clinical hold (~40% of pts discontinued PEGPH20), exclusion of pts at high risk for TE events and enoxaparin prophylaxis in both study arms. In Stage 2, randomization was 2:1 to PAG vs AG. Tumor HA was tested using a novel assay (VENTANA HA RxDx). Primary endpoints were PFS (evaluable pts) and TE event rate (Stage 2). Secondary endpoints were PFS by HA level and ORR. Results: 279 pts were randomized; 231 are evaluable for efficacy. Of 246 pts with HA data, 84 (34%) were HA-High. As of December 16, 2016, the primary PFS endpoint was statistically significant for PAG vs AG (HR 0.73, 95% CI 0.53-1.00; p = 0.048) (Table). PFS in HA-High pts was also statistically significant in the PAG vs AG arm (HR 0.51; 95% CI 0.26-1.00; p = 0.048). ORR in HA-High pts was 46% (PAG) vs 34% (AG). Overall survival in HA-High pts (exploratory) was 11.5 months (mo) (PAG) and 8.5 mo (AG) (HR 0.96, 95% CI 0.57-1.61). TE events were similar (PAG 14% vs AG 10%) following enoxaparin initiation. All grade treatment-related AE included peripheral edema (PAG 63% vs AG 26%), muscle spasms (56% vs 3%), neutropenia (34% vs 19%), and myalgia (26% vs 7%). Conclusions: Randomized Phase II study met both primary endpoints (PFS and TE event rate), with the largest improvement in the secondary endpoint of PFS in HA-High pts. These data support HA as a potential predictive biomarker for patient selection of PEGPH20, currently investigated in the ongoing global Phase III HALO 301 study with PFS and OS as co-primary endpoints. Clinical trial information: NCT01839487. [Table: see text]
Academic literacy and student diversity: The case for inclusive practice Ursula Wingate (2015) ISBN-13: 978-1783093472. Pp. 208. Genre-based automated writing evaluation for L2 research writing: From design to evaluation and enhancement Elena Cotos (2014) ISBN-13: 978-1137333360. Pp. 302.
It makes sense that writing studies scholars, from their position on the frontlines of academic writing support, would be among the first to notice graduate student needs around writing.In the 1980s, scholars began pointing out why this population of writers deserves more attention.Fast forward to today, popular
Results from a prototype real-time PCR assay that separately detected human papillomavirus genotype 16 (HPV16), HPV18, and 12 other carcinogenic HPV genotypes in aggregate (cobas 4800 HPV test) and results from a PCR assay that detects 37 HPV genotypes individually (Linear Array) were compared using a convenience sample of cervical specimens (n = 531). The percentage of total agreement between the two assays was 94.7% (95% confidence interval, 92.5 to 96.5%). The Linear Array test was more likely than cobas 4800 HPV test to test positive for the 12 other carcinogenic HPV genotypes among women without evidence of cervical disease (P = 0.004).
