8057 Background: BCD-021 demonstrated equivalence to Avastin in a comprehensive comparability exercise that included physicochemical, PK and PD studies, as well as phase I PK clinical study in patients with non-squamous NSCLC. Methods: 138 patients with advanced non-squamous NSCLC (stage IIIb/IV) were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks up to 6 cycles of therapy or until progression or unbearable toxicity. Results: ORR (primary endpoint) in both groups had no statistically significant differences: 42.59 % (95% CI 30.33 – 55.83) in BCD-021 group and 39.29% (95% CI 27.58 – 52.27%) in Avastin group. The lower limit of 95% CI for ORR difference between the groups (-14.96%) did not exceed the non-inferiority margin, hence BCD-021 is non-inferior to Avastin. There were also no differences between the groups for all other efficacy parameters: CR (1.85% vs 1.79%), PR (40.74% vs 37.50%), stable disease (51.85% vs 51.79%) and progression rate (5.56% vs 8.93%) in BCD-021 and Avastin group, respectively. AEs profiles of BCD-021 and Avastin were equivalent. Rate of all observed AEs including severe AEs had no statistically significant difference between the groups. Most AEs were associated with chemotherapy : neutropenia (85.29% vs 78,7%), anemia (88.24% vs 84.85%), leukopenia (79.41% vs 75.76%), thrombocytopenia (69.12% vs 62.12%), hyperglycemia (61.76 vs 56.06), LDH increase (48.53 vs 37.88), ALP increase (35.29% vs 30.30), ALT increase (26.47% vs 28.79%), alopecia (30.88% vs 24,24%), etc. Reactions specific for bevacizumab included: arterial hypertension (26,47% vs 22,73%), weakness (17.65 vs 16.67), lung bleeding (5.88% vs 3.03%), proteinuria (2.94% vs 0%), GIT perforation (0% vs 1.52%) and VTE (0% vs 1.52%). Binding and neutralizing antibodies were transient and detected only in 1 patient in each group that indicated to low immunogenic potential of both drugs. Conclusions: BCD-021 demonstrated non-inferiority to Avastin in patients with NSCLC. Clinical trial information: NCT01763645.

e20735 Background: Empegfilgrastim is an innovator drug product of pegylated G-CSF indicated for prophylaxis of neutropenia in patients receiving myelosuppressive chemotherapy. Methods: Objective was to compare safety and efficacy of a single dose of empegfilgrastim and daily dosing of filgrastim in patients receiving docetaxel 75 mg/m2 + doxorubicin 50 mg/m2. 135 patients with breast cancer were randomly assigned at a ratio of 1:1:1 to receive either single s.c. injection of empegfilgrastim at doses of 6 mg or 7.5 mg, or daily s.c. injections of filgrastim at a dose of 5 mcg/kg (until ANC ≥ 10x109/L). Results: At the cycle 1 mean duration of grade 4 neutropenia (primary endpoint) was significantly shorter in both empegfilgrastim groups: 0,905, 0,791 and 1,725 days in 6 mg, 7.5 mg and filgrastim groups, correspondingly. Mean difference in duration of grade 4 neutropenia between filgrastim and 7.5 mg groups was -0,934 d (95% CI -1,504 to -0,364 d) (p < 0,05). During the next 3 cycles duration of grade 4 neutropenia was also significantly shorter in both empegfilgrastim groups: cycle 2 (0.452, 0.326 and 0.925 d), cycle 3 (0.244, 0.310 and 0.641 d), cycle 4 (0.195, 0.475 and 0.892 d) (p < 0.05). Bacterial infections were observed only in 4 patients from filgrastim group, all patients were treated with oral anti-infective drugs. Empegfilgrastim at both doses was as safe and well tolerated as daily filgrastim administration. Most AEs were associated with chemotherapy. Frequency of G-CSF-specific reactions as all other AEs was equivalent in all groups: myalgia (7.14%, 4.65% and 4.65%), arthralgia (14.29%, 6.98% and 6.98%), ossalgia (9.52%, 9.30% and 4.65%), local reactions (7.14%, 2.33% and 2.33%). Conclusions: The results of this study demonstrated therapeutic superiority of empegfilgrastim, especially at a dose of 7.5 mg, compared to filgrastim. Clinical trial information: NCT02104830. Empegfilgrastim 6 mg Empegfilgrastim 7.5 mg Filgrastim p value Febrile neutropenia cycle 1 1 (2.38%) 1 (2.33%) 1 (2.50%) p > 0.05 all cycles 1 (2.38%) 3 (6.98%) 1 (2.50%) p > 0.05 Severe neutropenia cycle 1 31 (73.81%) 29 (67.44%) 35 (87.50%) p > 0.05 all cycles 40 (95.24%) 34 (79.07%) 40 (100.00%) p < 0.05

10502 Background: Doxorubicin (D) is the only approved first line therapy for most advanced soft tissue sarcomas (STS). Aldoxorubicin (A) consists of doxorubicin attached to an acid-sensitive linker that binds covalently to serum albumin. We compared the efficacy and safety of A to D as first line treatment for patients with advanced STS. Methods: 31 site international trial; 123 patients ages 18-78 years with histologically confirmed metastatic, locally advanced or unresectable STS randomized 2:1 to receive either 350 mg/m2 A (260 mg/m2 D equivalents) or 75 mg/m2D, every 3 weeks for a maximum of 6 cycles. Tumor response by CT was monitored every 6 weeks until completion of treatment, 2 months post treatment, then every 3 months to progression or withdrawal from study. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall response rate (ORR), PFS at 6 months and overall survival (OS). Both a blinded, independent review and an investigator site review were performed for each scan. Results: 83 patients were randomized to A and 40 to D. Groups were well-balanced for age, sex, race, performance status, and sarcoma pathology. Median (range) # of completed cycles: A = 6 (1-6); D = 4 (1-6). 30% of patients were from the U.S., 47% from Europe and 23% from Asia Pacific. Efficacy results are shown in the Table. Grade 3 or 4 adverse events that were increased in patients treated with A were neutropenia (28% vs 15%), nausea/vomiting (10% vs 0%), mucositis (12% vs 2 %), fatigue (5% vs 0%) and anorexia (4% vs 0%). LVEF < 50%: A = 0, D = 9.5%. Grade 3/4 pain was increased in the D arm (2% vs 8%). Grade 3/4 febrile neutropenia (17% vs 18%), anemia (17% vs 20%) thrombocytopenia (7% vs 5%) were similar for patients receiving A or D. Conclusions: Aldoxorubin is more efficacious than doxorubicin in the treatment of advanced STS with an acceptable safety profile. Clinical trial information: NCT01514188. Investigator review A D p PFS (months, median) 8.4 4.7 0.0002 HR (CI) 0.370 (0.212-0.643) 0.0004 PFS, 6 months 67.1% 36.1% 0.008 ORR (%) 24.0 5.3 CR 2.7 0 PR 21.3 5.3 Blinded independent review PFS (months, median) 5.7 2.8 0.018 HR (CI) 0.586 (0.358-0.960) 0.034 PFS, 6 months 46.8% 23.7% 0.038 ORR (%) 23 0 CR 0 0 PR 23 0