Amulirafusp alfa (IMM0306) consists of a fusion protein that incorporates the CD47-binding domain derived from signal-regulatory protein alpha (SIRPα) fused to a CD20 monoclonal antibody on each of the heavy chains. This investigation examined the safety profile and initial therapeutic activity of amulirafusp alfa in individuals with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Eligible participants included those with CD20-positive r/r B-NHL who had progressed after at least 2 prior treatment regimens. The dosing schedule began with a single administration of amulirafusp alfa during the initial 2-week period, followed by weekly intravenous infusions of the same dose during successive 4-week treatment cycles. Primary objectives focused on characterizing the agent’s safety, identifying the maximum tolerated dose (MTD), and establishing the recommended phase 2 dose (RP2D). From May 22, 2020, to February 10, 2022, the trial enrolled 48 patients with r/r B-NHL who received amulirafusp alfa at doses ranging from 40 to 2000 μg/kg. By the data cutoff of April 18, 2024, no dose-limiting toxicities had emerged, and the MTD had not been determined. The 2000 μg/kg dose level was selected as the RP2D. TRAEs of any grade affected all 48 patients (100%), while grade 3 or higher events were recorded in 33 patients (68.8%). The predominant grade 3 or higher TRAEs comprised lymphopenia (28/48, 58.3%), leukopenia (10/48, 20.8%), neutropenia (9/48, 18.8%), and anemia (5/48, 10.4%) and in the subgroup receiving 800–2000 μg/kg, objective response rates reached 41.2% (7/17, 95% confidence interval [CI] 18.4–67.1) among patients with follicular lymphoma and 33.3% (2/6, 95% CI 3.7–71.0) among those with marginal zone lymphoma. Amulirafusp alfa demonstrated an acceptable safety profile and encouraging early clinical activity in r/r B-NHL, thereby justifying continued development in subsequent studies.
