Evorpacept plus rituximab for the treatment of relapsed or refractory non-Hodgkin lymphoma: results from the phase I ASPEN-01 study

Abstract

CD47 overexpression has been associated with tumor cell survival. We present the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of evorpacept, a novel fusion protein comprising a high-affinity CD47–SIRPα immune checkpoint inhibitor to promote tumor-cell phagocytosis and inactive Fc domain to spare healthy cells, plus rituximab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) from the phase I ASPEN-01 study. Thirty-three patients received intravenous evorpacept (10 mg/kg [n=22] or 15 mg/kg [n=11] once weekly) until disease progression, in combination with fixed-duration intravenous rituximab (375 mg/m2 once weekly for 4 weeks, then every 4 weeks for 8 months). Evorpacept plus rituximab was well tolerated, with no doselimiting toxicities; no maximum tolerated dose was identified. The most common treatment-related adverse events (TRAE) were rash (24.2%) and fatigue (15.2%); most TRAE (70.0%) were mild-tomoderate in severity. Four (12.1%) patients reported grade 3 TRAE: anemia, neutropenia, decreased neutrophil count, increased alanine aminotransferase, decreased lymphocyte count, and decreased platelet count (one of each). Two (6.1%) patients experienced grade 4 TRAE (neutropenia, decreased neutrophil count). Six (18.2%) patients experienced serious AE (not treatment-related): asthma, dyspnea, respiratory failure, gastrointestinal infection, pneumonia, cardiac failure, and disease progression (one of each). Two (6.1%) deaths occurred (not treatment-related). Pharmacokinetics/pharmacodynamics were consistent with previous studies, with complete CD47 target occupancy (85%) achieved at both doses. In response-evaluable patients (n=32), objective response rate was 50.0% (95% confidence interval 33.1%– 69.8%). The safety, tolerability, and promising antitumor activity of evorpacept plus rituximab support continued evaluation of this combination in NHL (ClinicalTrials.gov identifier: NCT03013218).