Background MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin ® ; EU-bevacizumab). Objectives To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC).Patients and Methods This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EUbevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m 2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity. Results A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of −4.02 (90% CI −10.51 to 2.47; 95% CI −11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups. Conclusion MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles. Clinical trial registration EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.The members of the STELLA study investigators are listed in Online Resource 1 and in the Acknowledgements section.Extended author information available on the last page of the article care costs [1,2]. Avastin ® , the reference bevacizumab, has been approved for use in many cancer indications and settings, including first-line treatment of advanced NSCLC in combination with other chemotherapeutic agents [3,4]. Several international guidelines recommend the use of bevacizumab in association with chemotherapy in first-line and maintenance settings in advanced NSCLC [5,6]. In addition, recent evidence points to novel combinations of bevacizumab with new molecular therap...

This study established a trabectedin dose of 0.8 mg/m(2) combined with carboplatin AUC 4 and given every 4 weeks as the most feasible schedule in carboplatin-pretreated patients. Dose and cycle recommendations for carboplatin-naïve patients warrant further evaluation.

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Background: RTXM83 is a rituximab biosimilar candidate manufactured by MAbxience Company. Full spectrum of physicochemical and preclinical studies showed biosimilarity of RTXM83 and originator drug MabThera®/Rituxan® marketed by Roche. MabThera®/Rituxan® product is approved to treat Non-Hodgkin´s Lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis in the EU and US, plus it is approved to treat Diffuse Large B-cell lymphoma (DLBCL) in the EU. Rituximab is also used for other types of lymphoma (e.g. Mantle cell lymphoma) in certain parts of the word. Objective: To demonstrate comparable pharmacokinetics (PK) and safety profile (immunogenicity) to MabThera®, a clinical PK/immunogenicity analysis was designed to compare RTXM83 and MabThera® when administered with CHOP to patients with DLBCL. Methods: Analysis of an interim PK/Safety report from randomized and blinded study, where 24 patients with newly diagnosed DLBCL treated with R-CHOP as part of a multi-center study undertaken to assess the PK and immunogenicity. R-CHOP (rituximab-375mg/m2; cyclophopsphamide-750mg/m2; adriamycin-50mg/m2; vincristine-1.4mg/m2 on day 1 and prednisolone-60mg/m2 on days 1 to 5) was given every 3 weeks for a total of 6 cycles. The PK analysis were conducted on quality control (QC) checked analytical data for Cycle 1 and Cycle 6 using nominal blood sampling times. PK parameters were determined from the serum Rituximab concentration-time profiles obtained following administration of the first (Cycle 1) and last intravenous infusion of study medication (Cycle 6) using non-compartmental procedures in Phoenix WinNonlin (Version 6.2.1). The immunogenicity assessments were based on a specific and validated method for systematic evaluation of an unwanted immune response against RTXM83 and MabThera®. In fact, a confirmatory assay and specific cut point was established as current described recommendations in white papers and guidance documents. This part assures the assay sensitivity and a “characterization step” in the study sample analysis. A screening assay that picks up 5% positives that are subsequently shown to be due to non-specific binding in a confirmatory (immunodepletion) assay provides assurance that true low positives can be detected. Finally, the clinical immunogenicity measurements were performed on Cycle 5, Cycle 6 and follow-up patient samples. Results: Following the end of infusion of 375 mg/m2 q3w RTXM83 or MabThera® (Rituximab) (3 hours infusion) administered in combination with CHOP in Cycle 1 and Cycle 6, serum concentrations of Rituximab declined steadily in a generally bi-phasic manner. The arithmetic mean ±SD of PK parameters (T1/2(hrs); Cmax (ug/ml); Cmin (ug/ml); AUC0-∞ (ug*hrs/ml) of Rituximab during cycle 1, cycle 6 and follow-up patients were determined. All these data are comparable with values previously reported for rituximab in other conditions. No anti-drug antibody case was reported, so RTXM83 and MabThera® displaying null or undetectable immunogenicity. Conclusions: The data indicate that therapeutic levels of rituximab (RTXM83/Mabthera®) were observed across studied cycles. All data are comparable with values previously reported for rituximab. Therefore, PK profile and immunogenicity profile of RTXM83 is comparable with Mabthera® in treating DLBCL. Disclosures No relevant conflicts of interest to declare.

e20731 Background: MB02 is a bevacizumab biosimilar developed to stringent guidelines, including non-clinical and preclinical investigations and a clinical trial as first-line treatment in metastatic colorectal cancer (Romera A et al. Lancet Gastroenterol Hepatol 2018;3 (12): 845-855). A clinical trial (STELLA) has been initiated to confirm there are no clinically meaningful differences between MB02 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity (NCT03296163). Methods: STELLA study is a multinational, double-blind, randomized, parallel-group, equivalence study comparing the efficacy and safety of MB02 vs reference bevacizumab plus chemotherapy in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). Subjects aged 18-80 years, with ECOG status ≤1 and histologically confirmed NSCLC not receiving curative intent surgery or systemic therapy for advanced disease are randomized (1:1) to receive: chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) and either MB02 or reference bevacizumab 15 mg/kg every 3 weeks for up to 6 cycles (unless disease progression or treatment intolerance). Randomization is stratified by sex, smoking status, disease diagnosis (newly/recurrent), and stage. After 6 cycles, subjects can continue to receive MB02/reference bevacizumab in monotherapy every 3 weeks (until disease progression, treatment intolerance, death, withdrawal or end of study). The primary objective is to compare the objective response rate (ORR) between arms by week 18 (independently assessed) measured by RECIST v1.1. Progression free survival and overall survival (at 18 and 52 weeks), safety and immunogenicity will be assessed as secondary objectives. A sample size of 600 subjects was assumed providing about 89% power to show equivalence of MB02 plus chemotherapy with reference bevacizumab plus chemotherapy on a primary endpoint of risk ratio based on ORR. To date, 596 subjects have been recruited from more than 15 countries worldwide (Europe, Asia, Latin-America, Africa and Middle-East). At their last meeting in September, 2018 the independent data safety monitoring board (DSMB) recommended that the study continue without change. Clinical trial information: NCT03296163.

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