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Summary:Collection of peripheral stem cells by apheresis is a welldescribed process. Here, investigations concerning 'agglutination and flocculation' of stem cells collected from two patients are described. In both cases, cryoproteins were observed and cryofibrinogen was identified using highresolution two-dimensional electrophoresis. In one case, peripheral stem cells were collected after a second course of mobilization, and the cells were immediately washed at 371C before being frozen, allowing their use, despite the presence of cryofibrinogen. In the other case, 'agglutination' was reversed by warming the bag, and plasma was removed before freezing.

Background: Xentuzumab (Xen), an IGF-1/-2-neutralizing Ab, binds IGF-1 and IGF-2, inhibits their growth-promoting signaling, and suppresses AKT activation by everolimus (Ev). This Phase 1b/2 trial evaluates Xen in combination with Ev and exemestane (Ex) in HR+/HER2− LA/mBC. Methods: The two-arm, open-label, randomized Phase 2 part enrolled female patients (pts) with HR+/HER2− LA/mBC not amenable to curative therapy and refractory to nonsteroidal aromatase inhibitors. Pts were randomized (1:1) to: oral Ev (10 mg/d) + Ex (25 mg/d); or Xen (1000 mg/wk iv) + Ev (10 mg/d) + Ex (25 mg/d). Randomization was stratified by visceral metastases (VM; Y vs N). Treatment continued in 28-day cycles until progression, intolerable adverse events (AEs) or other reasons for discontinuation. Primary endpoint was progression-free survival (PFS), with an interim futility analysis incorporated in the study design. Results: Following the results of the interim analysis, the Data Monitoring Committee (DMC) advised early termination of the trial and discontinuation of Xen treatment. Thus, Xen treatment exposure time and time-to-event data for the Xen+Ev+Ex arm are limited. Of the 139 women treated (Xen+Ev+Ex 70; Ev+Ex 69), 77% had VM. Median PFS was not significantly different between arms (Xen+Ev+Ex vs Ev+Ex, 7.3 vs 5.6 months; HR [95% CI] 0.97 [0.57–1.65]; p=0.91). In a pre-specified subgroup of pts without VM, Xen+Ev+Ex showed favorable PFS vs Ev+Ex (HR 0.21 [0.05–0.98]; Pint=0.0141). Pint values <0.05 were also observed for ad hoc subgroups: measurable disease at baseline; bone-only metastases. Rates of total AEs/grade ≥3 AEs/drug-related AEs were similar between arms (Xen+Ev+Ex, 100/60/96%; Ev+Ex, 99/58/96%). The most common AEs overall were diarrhea (44 vs 33%), mucosal inflammation (39 vs 32%), rash (34 vs 33%) and stomatitis (34 vs 38%); most were grade 1/2. 6% of pts in the Xen+Ev+Ex arm discontinued Xen due to AEs. Ev/Ex discontinuations (Xen+Ev+Ex vs Ev+Ex) occurred in 13/6% vs 23/6%; 1 pt each in the Xen+Ev+Ex arm died from pneumonitis and liver injury and 1 pt each in the Ev+Ex arm died from Burkitt's lymphoma, acute kidney injury and metastases to the peritoneum. Conclusion: In the overall population, PFS did not improve with the addition of Xen to Ev+Ex and the trial was therefore discontinued early. Nevertheless, a favorable signal was observed in the pre-specified subgroup of pts without VM when treated with Xen+Ev+Ex, which warrants additional investigation. The safety profile was comparable between arms. Citation Format: Crown J, Sablin M-P, Cortés J, Bergh J, Im S-A, Lu Y-S, Martínez N, Neven P, Lee KS, Morales S, Pérez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero R-M, Bogenrieder T, Chin-Lun Huang D, Schmid P. Xentuzumab (BI 836845), an insulin-like growth factor (IGF)-neutralizing antibody (Ab), combined with exemestane and everolimus in hormone receptor-positive (HR+) locally advanced/metastatic breast cancer (LA/mBC): Randomized phase 2 results [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-01.