A phase 2/3 study of romiplostim N01 in chemotherapy-induced thrombocytopenia (CIT).

217 Background: CIT causes dose reduction or delay of chemotherapy (chemo), bleeding, and platelet (PLT) transfusion. This phase 2/3 study aimed to assess the efficacy and safety of romiplostim N01 in CIT. Methods: This trial comprising Part A (open-label) and B (randomized double-blinded) recruited patients (pts) with solid tumors or lymphoma and with CIT. In Part A, pts with a PLT count ≤200×10 9 /L before the day of chemo were included. Romiplostim N01 was injected subcutaneously per week (QW) for a 3-week chemo cycle at 1 μg/kg (group 1) or 2 μg/kg (group 2) for pts with a PLT count 100~200×10 9 /L, and at 2 μg/kg (group 3) for pts with a PLT count <100×10 9 /L. Primary endpoint was proportion of responders on the last day of chemo cycle, defined as pts who had an increase in PLT count of ≥30×10 9 /L from baseline for pts with a PLT count 100~200×10 9 /L, and an increase in PLT count of ≥30×10 9 /L or a PLT count ≥100×10 9 /L for pts with a PLT count <100×10 9 /L. In Part B, pts with a PLT count 75~150×10 9 /L were included and randomized 2:1 to receive romiplostim N01 or placebo QW at 2 μg/kg on day 1, and at 1 μg/kg on day 8 and 15 for two chemo cycles. Primary endpoint was proportion of responders, defined as pts resuming two consecutive chemo cycles without thrombocytopenia-induced dose modification (dose reduction by ≥15% or delay by ≥4 days or discontinuation) and without a rescue therapy. Results: In Part A, 50 pts were included between Mar 12, 2021 and Jul 29, 2021. The proportions of responders were 66.7% (10/15) in group 1, 53.3% (8/15) in group 2, and 90.0% (18/20) in group 3. Between Nov 8, 2022 and Jan 15, 2024, 63 pts were randomized in Part B. The proportion of responders in the romiplostim N01 group was significantly higher than that in placebo group (68.3% vs 40.9%). The adjusted rate difference was 27.6% (95% confidence interval [CI]: 2.1%, 50.2%). Treatment-related adverse events (TRAEs) occurred in 17 (41.5%) and 12 (54.5%) pts in the romiplostim N01 and placebo groups, of whom 1 (2.4%) and 0 were ≥grade 3. The most frequent TRAEs were nausea (12.2% vs 0), vomiting (12.2% vs 0), and increased aspartate aminotransferase (9.8% vs 4.5%). No treatment-related hemorrhage or death occurred. In pool analysis, the proportion of responders was 73.3% and 40.9% in pts treated with romiplostim N01 and placebo, respectively. The rate difference was 32.4% (95% CI: 9.2%, 52.9%). Conclusions: Romiplostim N01 showed promising efficacy and manageable safety in patients with CIT. Clinical trial information: PartA:NCT05851027 ; PartB:NCT05554913 . Pool analysis of Part A (pts with PLT count ≥75×10 9 /L) and Part B (all pts). Romiplostim N01 Placebo Rate Difference Part A+B (n=75) Part B (n=22) Romiplostim N01 (Part A+B) vs Placebo Lowest PLT count in Cycle 1, ×10 9 /L 85±41 59±32 / Highest PLT count in Cycle 1, ×10 9 /L 226±101 132±45 / Proportion of responders who completed the first chemo cycle without rescue therapy and without thrombocytopenia-induced dose modification of the second chemo cycle 55 (73.3%) 9 (40.9%) 32.4% 95% CI 61.9~82.9% 20.7~63.6% 9.2~52.9%