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Objective: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. Methods: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptorYpositive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety. Results: Seventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0Y31.4) versus 40 weeks (90% confidence interval, 16.3Y64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2. Conclusions: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

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9098 Background: AXL is an RTK implicated in epithelial-to-mesenchymal transition and as a resistance mechanism to multiple therapies including anti-PD1. Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods: This is a Phase II single-arm, two-Stage study with bemcentinib (200mg/d) and pembrolizumab (200 mg/q3wk) for previously treated, IO naïve pts (n = 48 in total) with Stage IV lung adenocarcinoma. The primary endpoint was ORR according to RECIST 1.1 with pre-defined minimum requirement for 18% RR in the first Stage (n = 24) to proceed to Stage 2. Secondary endpoints included DCR, PFS, OS and safety. Tumour biopsies were analysed for PD-L1 (22C3 pharmDx), AXL, and infiltrating immune cells. Results: Stage 1 completed enrolment in Apr ‘18. As of Feb ‘19, 38 pts (24 and 14 in Stage 1 and 2, respectively) have been dosed with the combination; median age 66 (range 39-79) yr, 59% male, all previously received one prior line of platinum-based chemotherapy or a licensed EGFR/ALK-directed therapy. The most common TRAEs (occurring in > 15% of pts) were transaminase increases (37%), diarrhoea (29%), and asthenia (17%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments. At time of writing, Stage 1 had met the efficacy threshold to proceed to Stage 2 with continued enrolment. Among 29 pts evaluable for response 7 PRs were reported (24%). For AXL positive pts (10/21 with available biopsies), ORR was 40%. PD-L1 status was known for 5 responders: 4 pts (80%) were PD-L1 negative or weakly positive. In Stage 1, mPFS was 4.0 months (95% CI 1.9 – NR) and 5.9 months in AXL positive pts (n = 10; 3.0 - NR). mOS was not mature. Conclusions: Overall, bemcentinib in combination with pembrolizumab was well tolerated and promising clinical activity was seen, particularly in pts with AXL positive disease. Updated results will be reported at the meeting, incl 12-month OS for Stage 1 and preliminary efficacy of Stage 2. Clinical trial information: NCT03184571.

The Nigerian Ministry of Health has been offering care for noma patients for many years at the Noma Children's Hospital (NCH) in Sokoto, northwest Nigeria, and M edecins Sans Fronti eres has supported these initiatives since 2014. The comprehensive model of care consists of four main components: acute care, care for noma sequelae, integrated hospital-based services and communitybased services. The model of care is based on the limited evidence available for prevention and treatment of noma and follows WHO's protocols for acute patients and best practice guidelines for the surgical treatment of noma survivors. The model is updated continually as new evidence becomes available, including evidence generated through the operational research studies performed at NCH. By describing the model of care, we wish to share the lessons learned with other actors working in the noma and neglected tropical disease sphere in the hope of guiding programme development.keywords cancrum oris, model of care,

Precision planters are important machines in the regime of modern technological agriculture. Field conditions, seed metering system and machine operating parameters affect the pneumatic planter performance. The pneumatic planter was evaluated to determine the effect of three tillage levels (L 1 , L 2, and L 3 ) and four travel speeds (S 1 , S 2 , S 3 and S 4 ). The sowing uniformity of the planter was observed with respect to the horizontal distribution of seeds within a row and described by using the precision index (I p ), the multiple index (I mult ), the miss-seeding index (I miss ) and the quality of feed index (I qf ). The results revealed that the tillage levels (L) and travel speed (S) had a significant effect (p<0.05) on dependent variables. The maximum I miss (22.12%) was observed at L 1 and S 4 whereas the maximum I mult was observed at L 1 and S 1 . The mean values of missing-, multi-, quality-feed and precision indices were 5.14%, 5.833%, 89.03% and 17.85% at L 3 , respectively. The mean values of multi-index 17.59%, 14.44%, 12.40% and 10.18%, quality feed index 74.07%, 75.92%, 75.74% and 74.07% and precision indices 21.47%, 23.26%, 25.51% and 28.53% were at S 1 , S 2 , S 3 and S 4 , respectively. The study showed that maize could be seeding within an acceptable precise range by bed-type pneumatic planter subjected to the proper seedbed preparation level.

Objective:The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 – 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir (Zoval) among Pakistani population with the rapid virologic response (RVR2/4 weeks) with HCV infections.Methods:This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir (Zoval) 400 mg plus ribavirin (with or without peg interferon) for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics.Results:A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 ± 11.41 years. Out of 573 patients 535 (93.3%) were treatment naive, 26 (4.5%) were relapser, 7 (1.2%) were non-responders and 5 (1.0%) were partial responders. A rapid virologic response was reported in 563(98.2%) of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated.Conclusion:Sofosbuvir (Zoval) is effective and well tolerated in combination with ribavirin in HCV infected patients.

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