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1062 Background: IMP321 is a recombinant soluble LAG3-Ig fusion protein that binds to MHC class II molecules and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. The activation of the dendritic cell network with IMP321 the day after a low dose injection of a single agent chemotherapy may lead to stronger anti-tumor CD8 T-cell responses. We report initial results of the safety run-in of a randomized, placebo-controlled phase IIb trial in patients (pts) with hormone receptor positive (HR+) MBC receiving first-line weekly paclitaxel. Methods: In the safety run-in phase 15 pts with MBC received weekly paclitaxel (80 mg/m2; D1, D8, D15) in a four week cycle in conjunction with either 6 mg (n = 6; cohort 1) or 30 mg (n = 9, cohort 2) IMP321 injections s.c. (D2 and D16) for 6 cycles. Patients without progressive disease could continue with a maintenance phase of 12 additional injections of IMP321 every 4 weeks. Blood samples for pharmacokinetics and immuno-monitoring were taken in cycle 1 and 4 just before and after IMP321 injection. Results: In total 15 pts (median age 53 years) were enrolled between Jan 2016 and Oct 2016. No dose limiting toxicities have been reported. Cytokine release syndrome grade 1 was the only serious adverse event (SAE) related to IMP321 and occurred twice in the same patient. Grade 1 and 2 injection site reactions were the most common related AEs and occurred in 14 pts (93 %). A dose-dependent increase in serum IMP321 concentration was observed among the two dose levels with a Cmaxbetween 4 and 24 hours. Increased number of circulating monocytes, dendritic cells and increased activation were observed at both dose levels of IMP321, supporting the working hypothesis. Conclusions: The 30 mg s.c. IMP321 given every two weeks in combination with weekly paclitaxel is the recommended phase 2 dose which is used in the ongoing randomized placebo controlled phase II part of the study. Clinical trial information: NCT02614833.

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A 30-year old male was admitted to the hospital with extremely painful blueish discoloration of his toes. After clinical and laboratory evaluation the diagnosis of a blue toe syndrome due to primary antiphospholipid syndrome (APS) was made. Complete resolution of the blue toe syndrome occurred within 72 hours following 9 mg phenprocoumon. APS consists of the association of lupus anticoagulant or antiphospholipid antibodies with arterial or venous thrombosis, thrombocytopenia, and spontaneous abortion. The exact pathways leading to thrombosis are still unknown. Our group has previously proposed that membrane-associated immune complexes contribute towards clinical symptoms in the antiphospholipid syndrome. The case presented strengthens that concept.