The objectives of this study were to quantify the prevalence of vitamin D insufficiency and deficiency in pregnancy, explore associated risk factors and discuss the public health implications. The study used retrospective analysis of randomly selected data. This is the first report on serum vitamin D levels in an unselected multi-ethnic population of pregnant women collected between April 2008 and March 2009. Women with sufficient stored serum were randomly selected from among all women who delivered between April 2008 and March 2009. Serum vitamin D levels were determined using liquid chromatography coupled to tandem mass spectrometry. Vitamin D levels were analysed with respect to ethnicity (marking skin tone), calendar quartile, body mass index (BMI), trimester and parity. Deficiency was defined as <25 nmol L(-1) , insufficiency 25-75 nmol L(-1) and adequacy >75 nmol L(-1) . Three hundred and forty-six women were included and represented the total population regarding skin tone, quartile, BMI, gestation and parity. Overall, 18% [95% confidence interval (CI): 15-23%] of sample women had adequate vitamin D levels; 36% were deficient, 45% insufficient. Among women with dark skin, only 8% (95% CI: 5-12%) had adequate levels compared with 43% (95% CI: 33-53%) of those with light skin. Obese women were found have significantly lower vitamin D levels than non-obese women. Vitamin D deficiency and insufficiency are prevalent year-round among pregnant women in North West London, especially those with darker skin. Existing supplementation guidelines should be supported; however, other measures are required to improve status among all women.

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Adenosine is a strong immunosuppressive mediator often found at high extracellular levels in the microenvironment of most tumors. Blocking A2A receptors, predominantly expressed on tumor-infiltrating immune cells, is aimed at reversing the immunosuppressive effect of adenosine. EOS100850 is a potent and highly selective small molecule antagonist of the A2A receptor that remains active even at the high adenosine concentration found in tumors and that does not cross the blood-brain barrier. This multicenter FIH Phase I clinical trial (NCT02740985) assessed the safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary clinical activity of EOS100850 monotherapy in subjects with refractory solid tumors. Pharmacodynamic assessments were performed in peripheral blood and tumor biopsies with simultaneous determination of plasma PK. Twenty-one adult participants with advanced malignancies were treated with EOS100850 monotherapy. Cohorts of 3 participants each were evaluated at 20 and 40 mg QD or 40 mg BID administration. Six participants were subsequently tested at doses of 80 mg BID and at the maximum administered dose of 160 mg BID. All subjects had at least 1 prior regimen (median 3). PK analysis indicated dose-proportional increase of EOS100850 plasma exposures up to 80 mg BID while PD evaluations revealed prolonged and maintained A2AR inhibition over the dosing interval. The most common adverse events (&gt;15%) attributed to the investigational treatment included Grade 1-2 nausea, fatigue, vomiting, and liver enzyme abnormalities. No drug-related Grade 3-4 AEs and no dose-limiting toxicities were observed. As of the data cut off (15JAN20), stable disease was observed in 6 participants who remain on therapy, including head & neck cancers, endometrial cancers, and checkpoint inhibitor-refractory melanoma. Further evaluation is ongoing as monotherapy and in combination with pembrolizumab or chemotherapy in both immune checkpoint-naïve and -refractory patients. Citation Format: Laurence Buisseret, Sylvie Rottey, Johann de Bono, Manon Mossakowski, Brant Delafontaine, Thubeena Manickavasagar, Nuria Kotecki, Chiara Martinoli, Manfred Schneider, Olivier De Henau, Patricia Chevron, Joanne Lager, Jean-Pascal Machiels. First in human study with EOS100850, a novel potent A2A antagonist, shows excellent tolerance and clinical benefit in immune resistant advanced cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT152.