Efficacy and safety of romiplostim N01 in cancer treatment–induced thrombocytopenia: Results from a phase II off-label study in China

Abstract Cancer Treatment-induced Thrombocytopenia (CTIT) is a common adverse event during cancer therapy, contributing to treatment delays, dose reductions, or discontinuation, and increasing the risk of bleeding, platelet transfusion dependence, and healthcare costs. While platelet transfusion and chemotherapy modification remain standard approaches, pharmacologic options are limited. The Chinese Society of Clinical Oncology recommends recombinant human thrombopoietin (rhTPO), interleukin-11 (rhIL-11), and, to a lesser extent, thrombopoietin receptor agonists (TPO-RAs) such as romiplostim. Romiplostim N01, a novel TPO receptor agonist consisting of a recombinant Fc–peptide fusion protein, is manufactured by Qilu Pharmaceutical Co., Ltd (Jinan, China) and approved in China for immune thrombocytopenia (NMPA registration number: S20240013). This phase II study evaluated the efficacy and safety of Romiplostim N01 in patients with persistent CTIT. Patients with CTIT lasting ≥4 weeks were enrolled and received Romiplostim N01 once weekly at an initial dose of 3 μg/kg. Dose escalation was guided by baseline platelet count: increments of 1 μg/kg per week for baseline counts ≥50×10⁹/L, and 2 μg/kg for <50×10⁹/L. The maximum dose was 10 μg/kg. Treatment continued for 3 weeks or until platelet recovery (≥100×10⁹/L). Patients who responded could either resume chemotherapy and continue Romiplostim N01. Treatment was stopped if thrombosis or secondary hematologic malignancy occurred. The primary endpoint was achieving a platelet count ≥100×10⁹/L within 3 weeks. Secondary endpoints included changes in bleeding score, fatigue score (FACIT-F), health-related quality of life (HRQoL, SF-36), and adverse events. From August 2024 to July 2025, 21 patients were enrolled (median age 62 years; 15 females, 6 males), including 20 with solid tumors and 1 with hematologic malignancy. The most common cancers were colorectal (24%), gynecologic (19%), breast (19%), and lung (14%). Fourteen patients (67%) achieved the primary endpoint with a median time of 16 days (range, 6–21). Platelet counts increased significantly after one week of treatment (41±28×10⁹/L vs. 23±20×10⁹/L; P<0.001) and continued to rise at weeks two (76±59×10⁹/L; P=0.016) and three (134±92×10⁹/L; P=0.001). The overall platelet response rate defined as achieving ≥75×10⁹/L with ≥30×10⁹/L increase from baseline was 81%. At a median follow-up of 275 days (range, 231–367), 38% of patients maintained platelet counts ≥100×10⁹/L. Clinical bleeding improved in parallel with hematologic response, with a reduction in median bleeding score from 2 (range, 0–4) at baseline to 0 (range, 0–1) at week three. Fatigue scores (FACIT-F) improved significantly (14±3 to 9±2; P<0.001). HRQoL (SF-36) showed marked improvement in 8 of 9 domains, including physical functioning, role-physical, general health, vitality, social functioning, role-emotional, mental health, and health transition. Only bodily pain showed no significant change. Romiplostim N01 was well tolerated; one patient experienced transient dizziness, headache, and fatigue. No thrombotic events or serious adverse events were observed. These findings support Romiplostim N01 as a promising and well-tolerated treatment option for CTIT. It achieved rapid platelet recovery, improved bleeding symptoms, reduced fatigue, and enhanced patient-reported quality of life, without serious safety concerns. Larger, randomized trials with longer follow-up are warranted to confirm these preliminary results and to further define its clinical role in CTIT management.