Telpegfilgrastim for chemotherapy-induced neutropenia in patients with non-small cell lung cancer: a multicentre, randomized, phase 3 study

BACKGROUND: Chemotherapy-induced neutropenia (CIN) is usually managed by recombinant human granulocyte colony stimulating factor (rhG-CSF) and pegylated rhG-CSF (PEG-rhG-CSF). This study evaluated the efficacy and safety of telpegfilgrastim, a novel Y-shaped PEG-rhG-CSF, for CIN prophylaxis in patients with non-small cell lung cancer (NSCLC). METHODS: This was a multicentre, randomized, open-label, active-controlled non-inferiority study. Patients with NSCLC who received 1-4 chemotherapy cycles of docetaxel plus carboplatin were randomized 1:1:1 to receive telpegfilgrastim 2 mg, 33 µg/kg or control drug (rhG-CSF [Topneuter®] in cycle 1 of chemotherapy, rhG-CSF [Topneuter®] or PEG-rhG-CSF [Xinruibai®] per patients' choice in cycles 2-4 of chemotherapy). The primary endpoint was duration of grade 4 neutropenia in cycle 1 of chemotherapy. Secondary endpoints included duration of grade 4 neutropenia in cycles 2-4 of chemotherapy, incidence of febrile neutropenia (FN), duration and incidence of ≥ grade 3 neutropenia, dynamic change of absolute neutrophil count from baseline and safety. RESULTS: From October 16, 2020, to September 1, 2021, 133 patients were randomized to telpegfilgrastim 2 mg (n = 44), 33 µg/kg (n = 45) and control group (n = 44). In cycle 1 of chemotherapy, the mean duration of grade 4 neutropenia in telpegfilgrastim 2 mg, 33 µg/kg groups and control group were 0.02 day, 0.09 day and 0.16 day, respectively. The least square mean differences versus control group were -0.14 day [95% confidence interval [CI]: -0.35, 0.06] for telpegfilgrastim 2 mg group and -0.06 day [95% CI: -0.26, 0.15] for telpegfilgrastim 33 µg/kg group. which met the prespecified non-inferiority margin of 1 day. Incidence of grade 4 neutropenia, incidence of FN and duration of ≥ grade 3 neutropenia in cycles 1-4 of chemotherapy was similar between telpegfilgrastim groups and control group. Telpegfilgrastim was well tolerated, and the incidence of adverse events were comparable with control group. CONCLUSION: This study demonstrated that telpegfilgrastim 2 mg or 33 μg/kg was non-inferior to rhG-CSF (Topneuter®) and PEG-rhG-CSF (Xinruibai®) for the management of CIN in patients with NSCLC. In particular, a 2 mg fixed dose of telpegfilgrastim presents a more convenient administration option. TRIAL REGISTRATION: NCT04466137 , July 10, 2020.