Neutropenia In Cycle Research Articles

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

BackgroundF-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®).MethodsThis was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated.ResultsThe mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim.ConclusionsA single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC.Trial registrationClinicalTrials.gov: NCT04174599, on 22/11/2019.

Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer.

Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative

PurposeLimited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10–20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice.MethodsThis prospective, real-world, observational, multinational, multicenter study (December 2016–October 2019) recruited patients with solid tumors or Hodgkin’s/non-Hodgkin’s lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration).ResultsIn total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2–3, and 1% in cycles 4–6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia.ConclusionsOverall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician’s judgement.

Abstract P5-16-14: A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

Abstract Background: Neutropenia is common in patients receiving myelotoxic chemotherapy. F-627( efbemalenograstim alfa ), is a novel long acting dimeric granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This study was to evaluate the efficacy and safety of F-627 for reducing chemotherapy-induced neutropenia as compared with filgrastim (GRAN®). Methods: This was a multicenter, randomized, open-label, and active-controlled non-inferiority study. Thirteen centers enrolled 239 patients who received chemotherapy with epirubicin (100mg/m2) and cyclophosphamide (600 mg/m2) (EC therapy) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 3 either a single 20 mg subcutaneous (s.c.) injection of F-627 per cycle or daily s.c injections of filgrastim 5 μg/kg/day. The primary endpoint was the duration of grade 3 (ANC <1× 109/L) or 4 (ANC<0.5× 109/L) neutropenia in cycle 1. The safety profile was evaluated. Results: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.67 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimator of the median difference between groups (F-627 − Filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of one-sided 97.5% CI was 0 days, which was within the 1-day prespecified non-inferiority margin. Results for all efficacy end points in cycles 2−4 was consistent with the results from cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed with F-627 compared with filgrastim. The nadir in the F-627 group was higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as multiple daily doses of filgrastim. The most frequently reported adverse events considered to be related to the study drug were bone pain and back pain. No deaths occurred during the study. 5.0% of F-627 patients and 6.7% of filgrastim patients reported serious adverse events (SAEs). The incidence of SAEs was low in both groups and no SAEs were related to study drugs, and were resolved during the study. Conclusions: A single fixed dose of 20 mg of F-627 was as safe and effective as multiple daily doses of filgrastim 5μg/kg/day in reducing chemotherapy-induced neutropenia and its complications in patients who received four cycles of EC therapy. F-627 provides the Chinese oncologists an alternative for simplifying the management of chemotherapy-induced neutropenia. The study was approved by the National Medical Products Administration of China (registration number: 2017L04033), and was registered on www.chinadrugtrials.org.cn (registration number: CTR20170705) and ClinicalTrials.gov (registration number: NCT04174599). Citation Format: William Daley, Zhimin Shao, Qingyuan Zhang, Hongshen Li, Changshen Ye, Shufang Wang, Langxi Zhang, Gaochong Zhang, Jianmin Chen. A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-14.

Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors

Prevention of chemotherapy-induced neutropenia (CIN) and its clinical consequences is an unmet need for which plinabulin, a selective immunomodulating microtubule-binding agent, is being tested. To demonstrate noninferiority between plinabulin and pegfilgrastim for days of severe neutropenia in cycle 1 in patients with solid tumors treated with docetaxel. The Plinabulin vs Pegfilgrastim for the Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors (PROTECTIVE-1) double-blind phase 3 randomized clinical trial was performed in multiple centers in China, Russia, Ukraine, and the US. Participants included patients with breast, prostate, or non-small cell lung cancer treated with single-agent docetaxel chemotherapy. Data were collected from June 1, 2018, to January 31, 2019. The database was locked on February 18, 2021. Data analysis was based on intention to treat and safety and performed from October 5, 2018, to February 23, 2021. Plinabulin, 40 mg, plus placebo or pegfilgrastim, 6 mg, plus placebo. The primary end point was day of severe neutropenia in cycle 1. Additional end points included clinical consequences of CIN (febrile neutropenia, hospitalizations, infections, antibiotic use, and modifications of chemotherapy dose), patient-reported outcomes for bone pain score, markers for immune suppression (neutrophil-to-lymphocyte ratio [NLR] of >5), immature neutrophils (band, promyelocyte, and myelocyte counts >0), and safety. Among the 105 patients included in the analysis (65 [6.19%] women; median age, 59 [range, 31-81] years), the primary end point was met within a noninferiority margin of 0.65 days, with a mean difference of 0.52 days (98.52% CI, 0.40-0.65 days). Grade 4 neutropenia frequency in cycle 1 was not significantly different. Plinabulin had earlier onset of action with less grade 4 neutropenia in week 1 of cycle 1. Plinabulin had fewer adverse clinical consequences with rates of febrile neutropenia (0 of 52 vs 1 of 53 [1.9%]), infections (4 of 52 [7.7%] vs 8 of 53 [15.1%]), chemotherapy dose delay of more than 7 days (2 of 52 [3.8%] vs 3 of 53 [5.7%]), and permanent chemotherapy discontinuation (7 of 52 [13.5%] vs 14 of 53 [26.4%]). Patients receiving plinabulin had significantly less bone pain (difference, -0.67 [95% CI, -1.17 to -0.16]; P = .01) and a better immunosuppressive profile (NLR >5 at day 8, 2 of 52 [3.8%] vs 24 of 51 [46.0%]; P < .001). Plinabulin was well tolerated, with comparable safety to pegfilgrastim. Plinabulin has comparable efficacy to pegfilgrastim for the prevention of CIN, with better safety and a better immunosuppressive profile. Plinabulin's same-day dosing compared with pegfilgrastim's next-day dosing offers distinct advantages, including reducing use of health care services. ClinicalTrials.gov Identifier: NCT03102606.

Comparison of Immunogenicity between the Proposed Pegfilgrastim Biosimilar MYL-1401H and Reference Pegfilgrastim

Introduction: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is indicated for reduction of incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. Here, the immunogenicity data for MYL-1401H, a proposed biosimilar of pegfilgrastim, from the clinical studies will be presented.Methods: The efficacy, safety, and immunogenicity of MYL-1401H were investigated in 3 clinical studies, 2 in healthy volunteers (HV) and 1 in patients receiving chemotherapy. MYL-1401H-1001 was a 3-way crossover study comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 2-mg dose of MYL-1401H with reference pegfilgrastim (Neulasta®) sourced from both the European Union (EU) and United States (US) in HV. MYL-1401H-1002 was a parallel-group study designed to compare the immunogenicity of MYL-1401H with US-pegfilgrastim at a repeated 6-mg dose in HV. MYL-1401H-3001 was a multicenter, randomized, double-blind, parallel-group equivalence study of MYL-1401H 6 mg vs EU-pegfilgrastim 6 mg in patients with breast cancer receiving chemotherapy for 6 cycles. The primary efficacy endpoint in MYL-1401H-3001 was duration of severe neutropenia in cycle 1, defined as days with absolute neutrophil count <0.5 × 109/L. A thorough assessment of immunogenicity was conducted across the 3 studies. The antidrug antibody (ADA; Covance, Chantilly, VA) analysis was performed using a validated, sensitive, and specific analytical method on the MesoScale Discovery® Platform (Rockville, MD). Serum samples were analyzed for the presence of ADA against MYL-1401H, EU-pegfilgrastim, and US-pegfilgrastim. Samples that resulted positive in the screening assay were further evaluated in a confirmatory assay. The samples confirmed as ADA positive were titrated to elucidate relative levels of the ADA response and further evaluated for domain characterization to determine if the antibodies were specifically directed against the polyethylene glycol (PEG) or the G-CSF domain of the molecule, or both. Samples confirmed as positive for ADA were analyzed for neutralizing antibodies (NAb; CIRION BioPharma Research) using a validated cell-based assay.Results: Overall, these studies demonstrated that the PK, PD, efficacy, and safety of MYL-1401H were equivalent to reference pegfilgrastim. Across all 3 studies, the proportions of subjects who were ADA positive before dosing were similar in the MYL-1401H (30/223; 13.5%) and EU-pegfilgrastim groups (16/139; 11.5%) and were lower in the US-pegfilgrastim group (4/97; 4.1%). Most (86.0%) of the subjects with ADA had antibodies that recognized the PEG domain, which may be attributable to exposure to PEG-related compounds in the environment as well as the highly sensitive nature of the assay, which can detect very low levels of antibodies. Treatment-induced impact on immunogenicity across the 3 studies was evaluated by analyzing the postdose ADA results excluding those subjects who were ADA positive at baseline (Table). Overall, the proportions of subjects with postdose treatment-induced ADA were similar in the MYL-1401H (20/192; 10.4%) and EU-pegfilgrastim groups (17/123; 13.8%), while they were higher in the US-pegfilgrastim group (28/93; 30.1%). Although the proportion of subjects with treatment-induced ADA was higher in the US-pegfilgrastim group, in most cases, the ADA recognized only the PEG moiety, the titers were low, and the antibodies were non-neutralizing. Two subjects (1 each in the MYL-1401H and EU-pegfilgrastim groups) had antibodies against the G-CSF moiety only. Two subjects were NAb positive in the MYL-1401H group, while none were NAb positive in either reference pegfilgrastim group. There was no evidence of loss of efficacy or severe treatment-induced immune-related adverse events in ADA- or NAb-positive subjects.Conclusion: Results in HV indicate that MYL-1401H does not induce either early or late immune response and has a low immunogenic potential, similar to that of EU- and US-pegfilgrastim, after repeated administration in a sensitive population without any confounding illness or immunosuppressive medications. Similarly, the immunogenic potentials of MYL-1401H and EU-pegfilgrastim are low in patients with breast cancer. Overall, MYL-1401H has an immunogenic profile similar to that of EU-pegfilgrastim and US-pegfilgrastim. [Display omitted] DisclosuresWaller:Mylan: Consultancy, Honoraria. Ranganna:Mylan Pharmaceuticals Inc: Employment. Pennella:Mylan: Employment. Mattano:HARP Pharma Consulting, LLC: Employment. Loa:Mylan Pharmaceuticals Inc: Employment. Donnelly:Mylan Pharmaceuticals Inc: Employment. Liu:Mylan Pharmaceuticals Inc: Employment. Watson:Covance: Employment. St-Jean:CIRION BioPharma Research Inc: Employment. Chatterjee:Biocon Research Ltd: Employment. Nayak:Biocon Research Ltd: Employment. Sengupta:Biocon Research Ltd: Employment. Kothekar:Biocon Research Ltd: Employment. Barve:Mylan Pharmaceuticals Inc: Employment.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies: a real-world study.

BackgroundChemotherapy-induced neutropenia is commonly encountered in clinical practice. The management of neutropenia has been evolving from short-acting granulocyte colony-stimulating factors (G-CSFs) to long-acting G-CSFs. However, an evaluation of the safety and effectiveness of long-acting G-CSFs in clinical practice is still lacking.MethodsThis multicenter, non-interventional study was aimed at exploring the safety and effectiveness of mecapegfilgrastim in different cancer patients in China. All patients provided written informed consent prior to the study and were treated according to routine clinical practice. Different prophylactic strategies (primary or secondary prophylaxis) were also compared.ResultsThis study included 638 patients from May 2019 to November 2020. More than half of the participants were breast cancer patients. The mean age of all the patients was 56 years. White blood cell increase (6.2%) was the most frequently reported adverse event (AE) possibly related to the study drug. No unexpected AEs were reported. Grade ≥3 neutropenia in chemotherapy treatment cycle 1 was reported in 36 (5.6%) patients. Incidence of grade ≥3 neutropenia in cycle 1 in the primary and secondary prophylaxis subgroups were of 4.3% and 9.2%, respectively. A decreasing trend of severe neutropenia incidence was observed from cycle 1 to cycle 4.ConclusionsMecapegfilgrastim was generally well tolerated, and no unexpected AEs were observed in this study. Primary administration of mecapegfilgrastim led to a lower incidence of neutropenia than did secondary administration. Continuous administration of mecapegfilgrastim could keep the incidence of neutropenia to a relatively low level.

Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study

BackgroundLipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia.Patient and methodsOne hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21.ResultsLipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was − 0.3 days (95% confidence interval, − 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 109/L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 109/L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease.ConclusionsThis study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile.Trial registration numberClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23

909P Efficacy and safety of HHPG-19K for prophylaxis of chemotherapy-induced neutropenia in patients with lymphoma

Neutropenia is a common complication of chemotherapy, which will lead to the delay or reduction of chemotherapy and affect the therapeutic effect. Mecapegfilgramtim (code name HHPG-19K), the novel long-acting rhG-CSF, has been developed. This study was evaluated the efficacy and safety of HHPG-19K for reducing neutropenia compared with un-prevention. This was a randomized, controlled non-inferiority study. A total of 151 lymphoma patients who were eligible for chemotherapy were randomly assigned into two groups, which received HHPG-19K fixed dosage of 6 mg or un-prevention in the first cycle of chemotherapy. The primary endpoint was the duration of grade≥3 neutropenia in cycle 1, incidence of grade≥3 neutropenia, and febrile neutropenia (FN). The safety profile was also evaluated. The adjusted mean duration of grade>1 neutropenia was 5 days in HHPG-19K fixed dosage of 6 mg group and 7 days in the un-prevention group (P<0.01). There was difference between the two groups in the incidence of grade≥3 neutropenia (P<0.01). There were 10 patients (12.82%) in HHPG-19K fixed dosage of 6 mg/kg group, 15 patients (20.55%) in un-prevention group experienced grade≥3 neutropenia. Compared with un-prevention group, the incidence of grade 4 neutropenia was significantly lower in patients treated with HHPG-19K fixed dosage of 6 mg/kg (7.69% vs 15.07%). For the incidence of FN, there were 5 patients (6.41%) in HHPG-19K fixed dosage of 6 mg/kg group, 11 patients (15.07%) in un-prevention group experienced FN (P<0.05). For safety profile, HHPG-19K group were all well-tolerated. The frequent AEs were ostalgia (13.70 vs 6.41%), fever (24.66% vs 11.54%), nausea (21.92% vs 1.28%), emesis (16.44% vs 1.28%), weakness (9.59% vs 2.56%) and others (19.18% vs 10.26%) during the chemotherapy, which were inferior to the un-prevention group (P<0.01). The frequent AEs were ostalgia (6.41 vs 13.70%), fever (11.54% vs 24.66%), nausea (1.28% vs 21.92%), emesis (1.28% vs 16.44%), weakness (2.56% vs 9.59%) and others (10.26% vs 19.18%) during the chemotherapy, which were inferior to the un-prevention group (P<0.01). No unexpected AE was observed. This study provided new evidence for HHPG-19K, which would be a new alternative clinical practice for prophylaxis of chemotherapy induced neutropenia.

Preoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant Chemotherapy.

Purpose: The aim of this study is to evaluate the risk factors for ≥ grade 3 neutropenia in gastric cancer patients receiving postoperative adjuvant chemotherapy.Methods: This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. Baseline and clinicopathological characteristics of the patients were collected. Patients were followed-up for 12 months and the incidence of neutropenia were recorded. Factors associated with neutropenia of chemotherapy in cycle 1 were investigated.Results: A total of 202 patients with gastric cancer were included. All patients received oxaliplatin plus oral capecitabine (CAPEOX) as the adjuvant chemotherapy. The incidence of ≥ grade 3 neutropenia is 11.9% (24/202) in cycle 1 among all patients. In multivariate analysis, independent risk factors for ≥ grade 3 neutropenia were serum prealbumin level (p = 0.041), prognostic nutritional index (PNI) (p = 0.049) and pre-cycle neutrophil count (p = 0.007).Conclusions: Our findings for the first time showed that nutritional parameter as prealbumin level and PNI are independent risk factors for neutropenia in gastric cancer patients receiving adjuvant chemotherapy. This may provide evidence for further investigation on prophylaxis use of granulocyte colony-stimulating factor in selected high-risk patients to prevent sever neutropenia in cycle 1 of adjuvant chemotherapy.

Mecapegfilgrastim in Chemotherapy-Induced Neutropenia: A Profile of Its Use in China.

Mecapegfilgrastim (HHPG-19K) is a long-acting pegylated recombinant human granulocyte-colony stimulating factor (rhG-CSF) that is administered subcutaneously as prophylaxis once per chemotherapy cycle as a weight-adjusted dose of 100µg/kg or as a 6mg fixed dose. It is approved in China to reduce the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer therapy associated with a clinically significant incidence of febrile neutropenia. In phase III trials, once per cycle prophylaxis with mecapegfilgrastim was more effective than placebo in reducing the incidence of grade ≥3 neutropenia in cycle 1 in patients with advanced non-small cell lung cancer and was more effective than filgrastim at reducing the mean duration of grade ≥3 neutropenia in cycle 1 in patients with breast cancer. The tolerability and safety profiles of mecapegfilgrastim were similar to those of filgrastim, with no unexpected adverse events (AEs); most adverse reactions in cycle 1 were mild or moderate in severity. Thus, mecapegfilgrastim is an effective and generally well tolerated treatment option for patients with non-myeloid malignancies receiving myelosuppressive chemotherapy, and extends the options available for managing chemotherapy-induced neutropenia in China.

Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial.

Neutropenia is a common complication from chemotherapy. Mecapegfilgramtim (code name HHPG-19K), a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), has been developed. This study was to evaluate the efficacy and safety of mecapegfilgrastim for reducing neutropenia compared with filgrastim. This was a randomized, controlled non-inferiority study. A total of 339 breast cancer patients who were eligible for (neo) adjuvant chemotherapy were randomized assigned into three groups to receive mecapegfilgrastim 100 µg/kg, mecapegfilgrastim fixed dose of 6 mg or filgrastim 5 µg/kg/day in the first cycle of chemotherapy. The primary endpoint was the duration of grade ≥3 neutropenia in cycle 1. The secondary endpoints included the duration of grade ≥3 neutropenia in cycles 2-4, incidence of grade ≥3 neutropenia, and febrile neutropenia (FN). The safety profile was also evaluated. The mean duration of grade ≥3 neutropenia was 1.06 [95% confidence interval (CI): 0.65, 1.26] days in mecapegfilgrastim 100 µg/kg group, 1.23 (95% CI: 0.84, 1.88) days in mecapegfilgrastim 6 mg group, and 2.06 (95% CI: 1.66, 2.46) days in the filgrastim group. The mean difference between mecapegfilgrastim 100 µg/kg and filgrastim was -1.00 (95% CI: -1.52, -0.48), the mean difference between mecapegfilgrastim 6 mg and filgrastim was -0.83 (95% CI: -1.36, -0.30). The upper bounds of 95% CI for the difference between mecapegfilgrastim and filgrastim were all <1 day (the predefined non-inferiority margin). For the incidence of grade ≥3 and grade 4 neutropenia, the mean duration of grade 4 neutropenia, mecapegfilgrastim showed better performance compared with filgrastim. For the incidence of FN, there was no difference between patients treated with mecapegfilgrastim and filgrastim. For safety profile, mecapegfilgrastim of two doses groups were all well-tolerated. Fixed 6 mg dose of mecapegfilgrastim exhibited comparable efficacy and safety in comparison with 100 µg/kg during 4 cycles. Long-acting mecapegfilgrastim (100 µg/kg and fixed 6 mg) is very effective and well tolerated when administered in the primary prophylaxis of chemotherapy induced neutropenia and in consecutive-cycle treatment. In some clinical parameters, mecafilgrastim is non-inferior and even superior to filgrastim. The fixed 6 mg-dose regimen showed similar efficacy and safety profile compared with 100 µg/kg regimen, and would be the preference in clinical practice, due to the convenient once-per-cycle administration and high-degree treatment compliance for the patients. This study provided new evidence for the novel long-acting rhG-CSF, mecapegfilgrastim, which would be a new alternative for clinical practice for prophylaxis of chemotherapy induced neutropenia.

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

Pegfilgrastim is indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy. Here, safety and efficacy of MYL-1401H, a proposed pegfilgrastim biosimilar, were investigated as prophylaxis for chemotherapy-induced neutropenia. This was a phase 3, multicenter, randomized, double-blind, parallel-group equivalence trial of MYL-1401H vs European Union–sourced reference pegfilgrastim. Patients with newly diagnosed stage II/III breast cancer eligible to receive (neo) adjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide every 3 weeks for 6 cycles were enrolled and randomized 2:1 to 6 mg of MYL-1401H or reference pegfilgrastim 24 h (+ 2-h window after the first 24 h) after the end of chemotherapy. The primary efficacy endpoint was the duration of severe neutropenia in cycle 1 (i.e., days with absolute neutrophil count (ANC) < 0.5 × 109/L). Mean (standard deviation (SD)) duration of severe neutropenia in MYL-1401H and reference pegfilgrastim groups was 1.2 days (0.93) and 1.2 days (1.10), respectively. The 95% CI for least squares mean difference (− 0.285, 0.298) was within the predefined equivalence range of ± 1 day. Secondary endpoints, including grade ≥ 3 neutropenia (frequency, 91% and 82% for MYL-1401H and reference pegfilgrastim, respectively), time to ANC nadir (mean (SD), 6.2 (0.98) and 6.3 (1.57) days), and duration of post-nadir recovery (mean (SD), 1.9 (0.85) and 1.7 (0.91) days) were comparable. Overall safety profiles of the study drugs were comparable. MYL-1401H demonstrated equivalent efficacy and similar safety to reference pegfilgrastim and may be an equivalent option for reducing incidence of neutropenia. (ClinicalTrials.gov, NCT02467868; EudraCT, 2014-002324-27).

Abstract P1-13-05: Efficacy and safety of eflapegrastim confirmed in reducing severe neutropenia in breast cancer patients treated with myelosuppressive chemotherapy in the second Phase 3 randomized controlled multinational trial compared to pegfilgrastim (RECOVER trial)

Abstract Background: Eflapegrastim is a novel investigational biologic comprised of recombinant human G-CSF covalently linked to the human immunoglobulin G4FC fragment using proprietary LAPSCOVERY™ technology with potentially unique distribution to areas rich in FcRn receptors. RECOVER is the second Phase 3 study to investigate the non-inferiority (NI) of eflapegrastim to pegfilgrastim in patients receiving chemotherapy for breast cancer. The first Phase 3 study, ADVANCE, has demonstrated the non-inferiority of eflapegrastim comparing to pegfilgrastim in the duration of severe neutropenia (DSN) in breast cancer patients receiving docetaxel and cyclophosphamide (TC) and was previously published at ASCO 2018 meeting. TrialDesign: Patients with Stage I to Stage IIIA breast cancer from centers in the USA, Canada, Poland, Hungary, South Korea and India were treated on Day 1 of each of four 21-day cycles with adjuvant or neo-adjuvant TC. On Day 2 of each cycle, patients received a single subcutaneous dose of either eflapegrastim 13.2 mg/0.6 mL (equivalent to 3.6 mg G-CSF) or pegfilgrastim (6 mg) in a 1:1 ratio. Patients had CBCs drawn on Day 1 prior to chemotherapy and Days 4-15 daily or until recovery of neutropenia in Cycle 1. CBC was also collected on Days 1, 4, 7, 10 and 15 in Cycles 2-4. The primary endpoint was to demonstrate the non-inferiority of eflapegrastim comparing to pegfilgrastim as measured by the mean DSN in Cycle 1 with NI margin of &amp;lt;0.62 day. Results: In a total of 237 intent-to-treat patients (randomized to 118 eflapegrastim; 119 pegfilgrastim), median age was 59 years (range 29 to 88 years); mean (SD) DSN was 0.31 (0.688) days for eflapegrastim and 0.39 (0.949) days for pegfilgrastim, demonstrating the non-inferiority (95% CI of ΔDSN: [-0.292, 0.129]; p&amp;lt;0.0001). Non-inferiority of eflapegrastim for DSN was maintained across all 4 cycles. There were no statistically significant differences in secondary endpoints: time to ANC recovery, depth of ANC nadir and incidence of FN at Cycle 1. The common Grade 3/4 adverse events observed in≥5%of patients were similar across both arms and were mainly hematologic including neutropenia, lymphopenia, anemia and leukopenia. Grade 3/4 bone pain and febrile neutropenia rates were similar across both arms and were less than 5%. Conclusions: Eflapegrastim, a novel long acting G-CSF demonstrated non-inferiority to pegfilgrastim in the reduction of DSN in breast cancer patients treated with TC and has validated the results from the first Phase 3 ADVANCE study. Eflapegrastim was safe and well-tolerated with a similar safety profile to pegfilgrastim. Citation Format: Schwartzberg L, Bhat G, Mezei K, Lang I, Moon YW, Senviratne L, Chawla S, Cobb P, Yang Z. Efficacy and safety of eflapegrastim confirmed in reducing severe neutropenia in breast cancer patients treated with myelosuppressive chemotherapy in the second Phase 3 randomized controlled multinational trial compared to pegfilgrastim (RECOVER trial) [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 P1-13-05.

Efficacy and safety of RGB-02, a pegfilgrastim biosimilar to prevent chemotherapy-induced neutropenia: results of a randomized, double-blind phase III clinical study vs. reference pegfilgrastim in patients with breast cancer receiving chemotherapy

BackgroundTreatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated G-CSF (Neulasta®, Amgen) with sustained release properties. This is a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen.MethodsTwo hundred thirty-nine women presenting with breast cancer were randomized to RGB-02 (n = 121) and the reference product (n = 118). All patients received up to 6 cycles of docetaxel/doxorubicin chemotherapy combination and a once-per-cycle injection of a fixed 6 mg dose of pegfilgrastim. Primary endpoint was the duration of severe neutropenia (ANC < 0.5 × 109/L) in Cycle 1 (2-sided CI 95%). Secondary endpoints included incidence and duration of severe neutropenia (in cycles 2–4), incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes.ResultsThe mean duration of severe neutropenia in Cycle 1 was 1.7 (RGB-02) and 1.6 days (reference), with a difference (LS Mean) of 0.1 days (95% CI -0.2, 0.4). Equivalence could be established as the CI for the difference in LS Mean lay entirely within the pre-defined range of ±1 day. This positive result was supported by the analysis of secondary endpoints, which also revealed no clinical meaningful differences. Safety profiles were comparable between groups. No neutralizing antibodies against pegfilgrastim were identified.ConclusionsTreatment equivalence in reducing the duration of chemotherapy induced neutropenia between RGB-02 and Neulasta® could be demonstrated. Similar efficacy and safety profiles of the once-per-cycle administration of RGB-02 and the pegfilgrastim reference were demonstrated.Trial registrationThe trial was registered prospectively, prior to study initiation. EudraCT number (2013–003166-14). The date of registration was 12 July, 2013.

Radium-223 in combination with paclitaxel in cancer patients with bone metastases: safety results from an open-label, multicenter phase Ib study

PurposeConcomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel.MethodsEligible patients had solid tumor malignancies with ≥2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m2 per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1).ResultsOf 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non–small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population.ConclusionRadium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.

Blinatumomab in Combination with Immune Checkpoint Inhibitors of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Preliminary Results of a Phase I Study

Background: Blinatumomab, a CD19/CD3 bispecific T cell engager antibody construct, leads to improved outcomes in patients with R/R CD19+ ALL compared to standard chemotherapy. However, most adults fail to achieve complete remission (CR) with blinatumomab, and the median duration of remission is only 7.3 months. Preclinical studies have shown significantly increased PD-L1 expression on leukemic blasts in patients who are refractory to or relapse after response to blinatumomab. Additionally, expression of the exhaustion markers PD-1 and TIM-3 on bone marrow (BM) CD3+ T cells is significantly higher among ALL patients than controls. The addition of PD-1 blockade +/- CTLA-4 blockade to blinatumomab and ALL blasts in vitro leads to increased T cell proliferation and enhanced blinatumomab-mediated cytotoxicity (Feucht et al, Oncotarget 2016). Thus, blockade of co-inhibitory pathways represents a viable strategy to enhance blinatumomab efficacy. We describe early results of a multi-center phase I study combining blinatumomab with monoclonal antibodies targeting PD-1 (nivolumab) +/- CTLA-4 (ipilimumab) in R/R CD19+ ALL.Methods: This phase I dose-escalation study evaluates the safety and tolerability (MTD) of blinatumomab in combination with nivolumab +/- ipilimumab using a 3+3 design. Patients ≥16 years-old with R/R CD19+ Pre-B ALL or MPAL are eligible including those with prior blinatumomab and/or prior allogeneic transplant (allo-SCT). Patients ≥60 years may be untreated and those 16-21 must be R/R to ³2 lines of therapy. The trial started at dose level (DL) A1 (Fig. 1). Upon determining the MTD for the combination of blinatumomab and nivolumab, dose escalation will add ipilimumab (DLB1). Patients may receive up to 5 cycles of blinatumomab and 1 year of nivolumab/ipilimumab. Patients achieving CR may proceed to allo-SCT. Patients removed from the study during the blinatumomab lead-in (days 1-10) will be replaced.Results: As of July 31, 2018, 8 adults (4 males/4 females) had enrolled at DLA1. The median age was 55 (range, 25-75) and baseline BM blast percentage was 73% (range, 8-98%). Baseline characteristics are presented in Figure 2. Seven patients received cytoreduction before treatment (6 steroids only and 1 steroids + Cytoxan). Two patients previously treated with blinatumomab were withdrawn from the study during the blinatumomab lead-in (1 for G3 pericardial effusion 2/2 disease progression and 1 for G3 hyperbilirubinemia). Among the 5 patients who received nivolumab to date, drug-related non-hematologic AEs of grade ≥3 included elevated AST (20%), ALT (20%), amylase (20%), and lipase (G4, 20%); hypophosphatemia (20%); rash (20%); infusion-related reaction (G4, 20%); and hypotension (20%). The elevated AST, ALT, amylase and lipase occurred prior to nivolumab dosing and resolved. One patient was removed from the study for a G4 infusion-related reaction following the 2nd dose of nivolumab that was considered a DLT. One patient in CR developed G4 neutropenia in cycles 2 + 3 but recovered spontaneously. Among the 5 evaluable patients, 4 (80%) achieved CR without MRD (2 after 1 cycle and 2 after 2 cycles of blinatumomab) with 3 ongoing remissions (median f/u 5 months) and 1 extramedullary relapse at day 125. Data on biomarkers including changes in T cell subpopulations in both BM and PB, and co-signaling molecule expression will be presented.Conclusions: Combination therapy with blinatumomab and nivolumab in R/R ALL with is feasible with acceptable toxicity. The MRD-negative CR rate was (80%) despite heavily pre-treated patients with significant baseline disease burden. The last patient treated at DLA1 is undergoing treatment before dose escalation to include ipilimumab. DisclosuresDeAngelo:Shire: Honoraria; ARIAD: Consultancy, Research Funding; Takeda: Honoraria; BMS: Consultancy; Amgen: Consultancy; Blueprint Medicines: Honoraria, Research Funding; Pfizer Inc: Consultancy, Honoraria; Glycomimetics: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Luznik:WIndMIL Therapeutics: Equity Ownership, Patents & Royalties. Gojo:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Merck inc: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

1696P - A randomized, open-label, non-inferiority study comparing the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B-cell non-Hodgkin lymphomas (B-NHL): AVOID neutropenia

Background: Lipegfilgrastim (LONQUEX®) has proven to be non-inferior to pegfilgrastim (NEULASTA®) in the reduction of the duration of severe neutropenia (DSN) in breast cancer patients. The efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with B-NHL at high risk for R-CHOP-21-induced neutropenia was investigated. The primary efficacy endpoint was the DSN in cycle 1. Methods: One hundred and one patients with NHL, median age of 74 years, were randomized to receive either 6 mg of lipegfilgrastim or pegfilgrastim per cycle during 6 cycles of R-CHOP-21. Results: Lipegfilgrastim was non-inferior to pegfilgrastim in the DSN in cycle 1: the mean DSN (days) in cycle 1 was 0.8±.96 and 0.9±1.08 in the per-protocol population, respectively with an adjusted mean difference (95% confidence interval) between groups of -0.3 (-0.70, 0.19). The upper boundary was below the predefined non-inferiority margin of 1. Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of febrile neutropenia (FN) in cycle 1 was 2% (1/41) in the lipegfilgrastim and 0% (0/44) in the pegfilgrastim group. The incidence of severe neutropenia in cycle 1 was similar in the lipegfilgrastim (21/41; 51%) and pegfilgrastim (23/44; 52%) groups. The mean time to absolute neutrophil count recovery to a threshold of ≥ 2.0 × 109/L was similar in lipegfilgrastim (8.3 days) and pegfilgrastim (8.7 days) groups. Adverse events (AEs) occurred in 98% of patients; in 45/46 of lipegfilgrastim and 49/50 of the pegfilgrastim group. Serious AEs occurred in 46% of patients; 21/46 in the lipegfilgrastim and 23/50 in pegfilgrastim group; none were assessed as treatment-related by the investigator. Fatal AEs occurred in 4% (2/46) of lipegfilgrastim and 10% (5/50) of the pegfilgrastim group. Study withdrawal due to AEs occurred in 2% (1/46) of the lipegfilgrastim and 18% (9/50) of the pegfilgrastim group. Conclusions: Lipegfilgrastim was non-inferior to pegfilgrastim in the reduction of the DSN in elderly patients with B-NHL. The safety of lipegfilgrastim was comparable to pegfilgrastim. Clinical trial identification: EudraCT: 2013-001284-23. Legal entity responsible for the study: Merckle GmbH (part of Teva Pharmaceuticals group). Funding: Merckle GmbH (part of Teva Pharmaceuticals group). Disclosure: H. Link: Advisory boards, investigator in sponsored trial: Teva. G. Illerhaus, U.M. Martens, A. Salar, R. Depenbusch, A. Kohler, M.M. Engelhardt, S. Mahlmann, M. Zaiss: Investigator in Teva sponsored trial. A. Lammerich, P. Bias, A. Buchner: Employee and stock options: Teva.

Effectiveness and Safety of Pegfilgrastim in BEP Treatment for Patients with Germ Cell Tumor.

The effectiveness and safety of pegfilgrastim during bleomycin, etoposide and cisplatin (BEP) chemotherapy have not yet been investigated. Patients with germ cell tumors (GCTs) who received pegfilgrastim during BEP at the Kanazawa University Hospital between January 2014 and December 2016 were retrospectively analyzed. The frequency of adverse events and effectiveness in inhibiting neutropenia were compared between cycles using pegfilgrastim and those using filgrastim. Pegfilgrastim and filgrastim were administered in 13 and 22 cycles, respectively. The absolute neutrophil count at the nadir was significantly lower in patients receiving pegfilgrastim than in those receiving filgrastim (p=0.003). The duration of grade 2-4 neutropenia in cycles using filgrastim was significantly longer than that in those pegfilgrastim (p=0.01). No significant differences in the incidence of febrile neutropenia and serious adverse events were observed. Pegfilgrastim can be safely and effectively administrated during BEP for patients with GCT.

1574P - Efficacy and safety of RGB-02, a proposed biosimilar pegfilgrastim to prevent chemotherapy-induced neutropenia: Results of a randomized, double-blind, phase III clinical study vs. reference pegfilgrastim in patients with breast cancer receiving docetaxel/doxorubicin

Background: Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02, a pegylated G-CSF (pegfilgrastim) developed by Gedeon Richter is a proposed biosimilar to the reference pegfilgrastim product Neulasta®. Here we are presenting the results of a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen (EudraCT nr: 2013-003166-14). Methods: 239 women presenting with breast cancer were randomized to RGB-02 (n = 121) and to the reference pegfilgrastim, Neulasta® (n = 118). All patients received up to 6 cycles of docetaxel/doxorubicin and a once-per-cycle injection of a fixed 6 mg dose of pegfilgrastim. Primary endpoint was the duration of severe neutropenia (ANC < 0.5 x109/L) in Cycle 1 (2-sided CI interval 95%). Secondary endpoints included incidence and duration of severe neutropenia, incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes. Results: The mean duration of severe neutropenia in Cycle 1 was 1.7 (RGB-02) and 1.6 days (reference), with a difference (LS Mean) of 0.1 days (95% CI -0.2, 0.4). Therapeutic equivalence could be established as the CI for the difference in LS Mean lay entirely within the pre-defined range of ± 1 day. The incidence of severe neutropenia decreased from cycle 1 to 2 in both groups with no statistical significant differences, for RGB-02 from 84.6% (99 patients) to 54.1% (60 patients) and from 77.0% (87 patients) to 43.7% (45 patients) in the comparator group. Both groups were similar regarding mean time to ANC recovery with 3.4 ± 1.84 days (RGB-02) and 3.7 ± 1.88 days (reference) during Cycle 1. Safety profiles were comparable between groups. Conclusions: Therapeutic equivalence and similar safety profiles between RGB-02 and Neulasta® as once-per-cycle administration could be demonstrated. RGB-02 can provide a biosimilar alternative for the prevention of neutropenia. Clinical trial identification: EudraCT nr: 2013-003166-14 Legal entity responsible for the study: Gedeon Richter Plc. Funding: Gedeon Richter Plc. Disclosure: K. Horvat-Karajz, A. Illes: Employee of Gedeon Richter Plc. All other authors have declared no conflicts of interest.