Abstract P5-20-03: A phase 2, double-blind, randomized, placebo-controlled, dose-finding study of sotatercept for the treatment of patients with chemotherapy-induced anemia and metastatic breast cancer.

Abstract

Abstract Background: Sotatercept is a recombinant activin receptor IIA (ActRIIA) ligand trap and is comprised of the extracellular domain of ActRIIA linked to the Fc domain of human IgG1 (ActRIIA-IgG1). Results of preclinical and early clinical studies provide evidence that sotatercept increases the concentration of hemoglobin (Hb) in blood and may constitute a novel treatment for chemotherapy-induced anemia (CIA), a condition that results in significant morbidity. Methods: This study evaluated the safety of, and hematopoietic response to, sotatercept in patients with CIA and metastatic breast cancer (MBC). Response was defined as increase in Hb ≥1 g/dL for ≥28 consecutive days during treatment or ≤2 months following the last dose, in the absence of red blood cell (RBC) transfusion or treatment with an erythropoiesis stimulating agent (ESA). If RBC transfusion or treatment with an ESA was required, no Hb measurements within 28 days of the RBC transfusion or administration of ESA were used to determine the Hb response. Subjects were randomized to subcutaneous injection of sotatercept (0.1, 0.3, or 0.5 mg/kg) or placebo and were treated on day 1 of each of four 28-day cycles. Results: Thirty (30) subjects were enrolled and treated (5 placebo, 25 sotatercept). Increases in mean Hb in the 0.3 and 0.5 mg/kg groups were greater than in 0.1 mg/kg and placebo groups. Increases peaked approximately 15 days following treatment and declined over the remaining interval between treatments. Among 23 subjects with confirmed CIA and administered ≥1 dose and followed for ≥57 days (per-protocol analysis), 5/18 (28%) administered sotatercept responded (0/5 [0%] at 0.1 mg/kg; 3/9 [33%] at 0.3 mg/kg; 2/4 [50%] at 0.5 mg/kg) vs 1/5 [20%] administered placebo. Among 13 nonresponders administered sotatercept, 5 (39%) experienced ≥1 dose interruption/reduction, as per protocol, due to elevated Hb. The incidence of adverse events (AEs) was consistent with that reported in patients with MBC. No dose-limiting or dose-related toxicity was observed. Conclusions: Sotatercept demonstrated dose-dependent hematopoietic activity in subjects with CIA and MBC. The safety findings were generally consistent with the known safety profile of sotatercept. These data suggest that a greater dose of sotatercept or a dose interval <28 days might result in a more sustained, and greater rate of, hematopoietic response. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-03.