Open-label, phase 2 study of roxadustat for treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies.

12085 Background: Anemia is prevalent in patients (pts) receiving myelosuppressive chemotherapy (> 60%) and exacerbated by repeated treatment cycles due to cytotoxic agent accumulation. Chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in pts with anemia receiving myelosuppressive chemotherapy. Methods: This open-label, single-arm, proof-of-concept Phase 2 study included pts with mostly advanced, non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had not received red blood cell (RBC) transfusion or erythropoietin-stimulating agents within 4 weeks of enrollment. Patients were treated with oral roxadustat for ≤16 weeks. The primary efficacy endpoint was maximum mean change in Hb within 16 weeks of baseline without RBC transfusion in pts who had received ≥1 dose of roxadustat and who had a baseline and ≥1 post-dose Hb assessment. Hb response and safety data were preliminarily assessed in pts receiving a starting dose of 2.0 mg/kg thrice weekly (TIW) for 4 weeks: doses of 100, 150, and 200 mg were given to pts weighing < 70, 70–100, and > 100 kg, respectively. Following a review of data from these pts, dose was increased to 2.5 mg/kg—150, 200, and 250 mg TIW to pts weighing < 70, 70–100, and > 100 kg, respectively—and adjusted every 4 weeks from Week 5 based on Hb response. Results: Patients were assigned to 2.0 mg/kg (n = 31) and 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The maximum mean Hb change from baseline without RBC transfusion was 2.47±1.51 g/dL and 2.52±1.54 g/dL in the 2.0 mg/kg and 2.5 mg/kg cohorts, respectively. Hb increased by ≥1.5 g/dL in 73% of pts and ≥2.0 g/dL in 61% of pts. Median time to ≥2.0 g/dL Hb increase was 71.0 days. Both cohorts had higher proportions of pts with a Hb increase of ≥1, ≥1.5, or ≥2 g/dL at Week 16 compared with baseline. Median time to ≥1 and ≥2 g/dL Hb increase was shorter in pts who started on 2.5 mg/kg compared with 2.0 mg/kg doses (≥1 g/dL: 30 vs 44; ≥2 g/dL 57 vs 105, respectively). Fewer pts required an RBC transfusion (Week 5 to end of treatment) when starting on 2.5 mg/kg compared with 2.0 mg/kg doses (10.2% vs 20.0%). Subgroup analyses based on major tumor and baseline chemotherapy types demonstrated efficacy of roxadustat at both starting doses. The overall safety profile observed was consistent with the patient population under study. Overall, 92% of pts experienced an adverse event (AE). Most AEs were consistent with the underlying malignancies and chemotherapy regimens used. The incidence of deep vein thrombosis was 15.2% (n = 14) and pulmonary embolism was 9.8% (n = 9). There were 17 deaths (18.5%) during the study; none were attributed to roxadustat, and most were associated with disease progression. Conclusions: Roxadustat increased Hb in CIA regardless of tumor type and chemotherapy regimen. These data support additional clinical study. Clinical trial information: NCT04076943.