Nghiên cứu Giai đoạn I/II để đánh giá dược lực học lâm sàng và độ an toàn của liều đơn gia tăng và nhiều liều PF-06881894 qua đường tiêm dưới da ở phụ nữ mắc ung thư vú không di căn xa

Cancer Chemotherapy and Pharmacology - Tập 88 Số 6 - Trang 1033-1048 - 2021
Hsuan‐Ming Yao1, Sarah R. Jones2, S. Morales3, Shahrzad Moosavi4, Jeffrey Zhang1, Amy Freyman5, Faith D. Ottery6
1Pfizer Inc, Lake Forest, IL, USA
2Clinical Development and Operations, Pfizer Inc, Collegeville, PA, USA
3Hospital Universitario Arnau de Vilanova, Lleida, Spain
4Pfizer Inc., New York, NY, USA
5Pfizer Inc, Cambridge, MA, USA
6Ottery & Associates, LLC, Deerfield, IL, USA

Tóm tắt

Tóm tắt Mục đích

Đánh giá dược lực học (PD), dược động học (PK) và độ an toàn của liều đơn và nhiều liều PF-06881894 (pegfilgrastim-apgf; Nyvepria), một thuốc tương tự sinh học của pegfilgrastim tham chiếu (Neulasta®), ở phụ nữ mắc ung thư vú di căn không xa.

Phương pháp

Trong Giai đoạn I (Chu kỳ 0) của nghiên cứu Giai đoạn I/II này, đáp ứng PD (số lượng bạch cầu trung tính tuyệt đối [ANC]; số lượng CD34 + ), hồ sơ PK, và độ an toàn của một liều đơn 3 hoặc 6 mg PF-06881894 được đánh giá ở bệnh nhân chưa điều trị hóa trị trước khi phẫu thuật vú triệt để. Trong Giai đoạn II (Chu kỳ 1–4), đáp ứng PD (thời gian giảm bạch cầu trung tính nặng [DSN, Chu kỳ 1], ANC [Chu kỳ 1 và 4]) và hồ sơ PK (Chu kỳ 1 và 4) của liều đơn và nhiều liều 6 mg PF-06881894 sử dụng đồng thời với hóa trị và sau phẫu thuật vú triệt để được đánh giá.

Kết quả

Hai mươi lăm bệnh nhân (tuổi trung bình 59 năm) đã được ghi danh (Chu kỳ 0, n = 12; Các Chu kỳ 1–4, n = 13). Trong Chu kỳ 0, đáp ứng PD và giá trị PK thấp hơn với liều 3 mg so với 6 mg PF-06881894. Trong Các Chu kỳ 1 và 4, trung bình DSN là 0,667 ngày sau khi được tiêm đơn hoặc nhiều liều 6 mg PF-06881894 tương ứng. Trong Chu kỳ 4 so với Chu kỳ 1, các đáp ứng PD mạnh mẽ hơn; giá trị PK (diện tích dưới đường cong trung bình, nồng độ tối đa) thấp hơn; và giá trị độ thanh thải cao hơn. Hồ sơ độ an toàn của PF-06881894 tương tự như của pegfilgrastim tham chiếu.

Kết luận

PF-06881894 dưới dạng một liều đơn 3 hoặc 6 mg trước phẫu thuật triệt để, hoặc nhiều liều 6 mg/cycle sau phẫu thuật, với/không có hóa trị ức chế tủy xương, nhất quán với dược lý lâm sàng và hồ sơ độ an toàn của pegfilgrastim tham chiếu.

Đăng ký thử nghiệm

Tháng 10 năm 2017. Mã số Đăng ký ClinicalTrials.gov: NCT02650193. Số EudraCT: 2015-002057-35.

Từ khóa


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