Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim

Study Overview
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Brief Summary
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The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Detailed Description
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The Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare the proposed biosimilar LA-EP2006 with the reference pegfilgrastim in woman with early stage breast cancer receiving (neo)-adjuvant myelosuppressive chemotherapy. Patient received TAC (intravenous docetaxel 75mg/m^2, doxorubicin 50 mg/m^2, and cyclophosphamide 500mg/m^2) on day1 of each cycle, for six or more cycles. A total of 308 patients were randomized to LA-EP2006 (n=155) or reference Neulasta® (n=153). Treatment was given subcutaneously on day 2 of each cycle. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count <0.5 × 10^9 cells/L). LA-EP2006 was equivalent to the reference product in DSN (difference: -0.16 days; 95% CI [-0.40, 0.08]). Further, LA-EP2006 and the reference pegfilgrastim showed no clinically meaningful differences regarding efficacy and safety.

Official Title
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Pivotal Study in Breast Cancer Patients Investigating Efficacy and Safety of LA-EP2006 and Neulasta®

Conditions
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Chemotherapy-induced Neutropenia, Breast Cancer

Intervention / Treatment
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* Drug: LA-EP2006
* Drug: Neulasta®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically proven breast cancer eligible for six cycles of neoadjuvant or adjuvant chemotherapy Exclusion Criteria: concurrent or prior chemotherapy for breast cancer concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy concurrent prophylactic antibiotics previous therapy with any G-CSF (granulocyte-colony stimulating factor) product Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LA-EP2006<br>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. | Drug: LA-EP2006<br>* Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.<br>* Other names: pegfilgrastim;|
| Active Comparator: Neulasta®<br>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. | Drug: Neulasta®<br>* Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle Neulasta® is injected s.c. post chemotherapy application.<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy | Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9/l (grade 4 neutropenia). | 21 days (Cycle 1 of chemotherapy treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Febrile Neutropenia (FN) | FN was defined as oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN (febrile neutropenia, neutropenic sepsis) were taken into account. | across all cycles (18 weeks) | 
| Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles | Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once. | across al cycles (18 weeks) | 
| Depth of ANC Nadir in Cycle 1 | The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. | Cycle 1 (3 weeks) | 
| Number of Patients With ANC Nadir Per Day in Cycle 1 | Numbers of patients with ANC nadir based per day during Cycle 1 are given. | Cycle 1 (3 weeks) | 
| Time to ANC Recovery in Days in Cycle 1 | Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1. | across Cycle 1 (3 weeks) | 
| Frequency of Infections by Cycle and Across All Cycles | The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class Infections and Infestations. | across all cycles (18 weeks) | 
| Mortality Due to Infection | Number of patients with death due to infections | Study course (19 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pegfilgrastim, G-CSF, neutropenia, breast cancer, myelosuppressive chemotherapy