Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer

Hsuan-Ming Yao, Sarah Ruta Jones, Serafin Morales, Shahrzad Moosavi, Jeffrey Zhang, Amy Freyman, Faith D Ottery, Hsuan-Ming Yao, Sarah Ruta Jones, Serafin Morales, Shahrzad Moosavi, Jeffrey Zhang, Amy Freyman, Faith D Ottery

Abstract

Purpose: To evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of single and multiple doses of PF-06881894 (pegfilgrastim-apgf; Nyvepria™), a biosimilar to reference pegfilgrastim (Neulasta®), in women with non-distantly metastatic breast cancer.

Methods: In Phase I (Cycle 0) of this Phase I/II study, the PD response (absolute neutrophil count [ANC]; CD34 + count), PK profile, and safety of a single 3- or 6-mg subcutaneous dose of PF-06881894 were assessed in chemotherapy-naïve patients before definitive breast surgery. In Phase II (Cycles 1-4), the PD response (duration of severe neutropenia [DSN, Cycle 1], ANC [Cycles 1 and 4]) and PK profile (Cycles 1 and 4) of single and multiple 6-mg doses of PF-06881894 concomitant with chemotherapy and after definitive breast surgery were assessed.

Results: Twenty-five patients (mean age 59 years) were enrolled (Cycle 0, n = 12; Cycles 1-4, n = 13). In Cycle 0, PD responses and PK values were lower with 3-mg versus 6-mg PF-06881894. In Cycles 1 and 4, mean DSN was 0.667 days after single or multiple 6-mg doses of PF-06881894, respectively. In Cycle 4 versus Cycle 1, PD responses were more robust; PK values (mean area under the curve, maximum concentration) were lower; and clearance values were higher. The safety profile of PF-06881894 was similar to that for reference pegfilgrastim.

Conclusion: PF-06881894 as a single 3- or 6-mg dose prior to definitive surgery, or multiple 6-mg/cycle doses postoperatively, with/without myelosuppressive chemotherapy, was consistent with the clinical pharmacology and safety profile of reference pegfilgrastim.

Trial registration: October 2017. ClinicalTrials.gov Identifier: NCT02650193. EudraCT Number: 2015-002057-35.

Keywords: Biosimilar; Breast cancer; Chemotherapy; Myelosuppression; Neutropenia; Pegfilgrastim.

Conflict of interest statement

AF, SRJ, SM, H-MY, and JZ are full time employees of, and own stock or options, in Pfizer.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. Chemo, chemotherapy; PD, pharmacodynamics; PK, pharmacokinetics; SC, subcutaneous; SOC, standard-of-care; TAC, docetaxel, doxorubicin and cyclophosphamide chemotherapy
Fig. 2
Fig. 2
Pharmacological effects of a single ascending-dose of PF-06881894 over time in the absence of chemotherapy in Cycle 0. a ANC levels (FAS), b CD34+ (FAS), and c pegfilgrastim concentration (PK population). ANC, absolute neutrophil count; FAS, full analysis set; PK, pharmacokinetics
Fig. 3
Fig. 3
Pharmacological effects of multiple doses of PF-06881894 over time in the context of myelosuppressive chemotherapy in Cycles 1 and 4. a ANC levels (FAS) and b pegfilgrastim concentration (PK population). ANC, absolute neutrophil count; FAS, full analysis set; PK, pharmacokinetics

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