Preliminary results of a first-in-human phase I dtudy of IMM01, SIRPα Fc protein in patients with relapsed or refractory lymphoma.
Authors: Sun Mingyuan , Qi Junyuan , Zheng Weiwei , Song Lin , Jiang Bo , Wang Zhenzhen , Huang Cheng , Tian Wenzhi , Qiu Lugui 
Published: June 2021

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Background: IMM01 is a recombinant human signal regulatory protein α (SIRPα) IgG 1 fusion protein that exerts dual-mechanism antitumor activity via engagement of activating tumor cell phagocytosis and stimulating T-cell anti-tumor responses by binding CD47 on tumor cell membrane. IMM01 displays promising preclinical characteristics regarding its receptor occupancy/tumor exposure/efficacy relationship. Unlike anti-CD47 monoclonal antibodies, IMM01 shows unique property of weak human erythrocyte conjugation so as avoiding severe hemolysis. Methods: Monotherapy of IMM01 was conducted in 14 enrolled subjects with relapsed or refractory lymphoma who had failed standard therapies. Dose escalation was performed in routine design of accelerated single-patient followed by standard 3+3 to establish the preliminary data of safety as well as determination of a recommended expansion dosage. Each cycle contains 4 dosing weekly followed by a week rest. The tumor responses were evaluated based on Lugano Classification 2014. IMM01 pharmacokinetics (PK) and pharmacodynamics (PD) analyses were performed. Results: As of February 08, 2021, a total of 14 patients (median age 49 y; median prior therapy 3) were enrolled in 6 escalated dose cohorts (0.003 mg/kg, 0.01 mg/kg, 0.05 mg/kg, 0.15 mg/kg, 0.5 mg/kg and 1.0 mg/kg). The common tumor types were follicular lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma. No DLTs were observed up to 1.0 mg/kg. One SAE (grade 2 increased amylase and grade 3 increased lipase) was reported, which induced by disease progression on pancreas. The most common treatment related adverse events were thrombocytopenia (54%), neutrophil count decreased (36%), Pyrexia (36%) and Anaemia (27%). There were grade 1 or 2 except for one patient experienced a grade 3 platelet count decreased (lower baseline at 70×109/L). Transient platelet count decrease after 2 hours and return to baseline at 24 to 48 hours post first infusion. In 12 evaluated patients, one patient with FL had a CR and maintained a 26-week response at the dose of 0.01 mg/kg. One patient with HL who had failed PD-1 inhibitor was confirmed PR at 27 weeks and continues the therapy, and one patient with MZL maintained SD for 12 weeks at the dose of 0.15 mg/kg. One patient with HL failed PD-1 inhibitor and one patient with FL maintained a shrunk SD for 12 weeks at the dose of 0.5 mg/kg. One patient with AITL was evaluated as a shrunk SD after 5 doses treatment at the dose of 1.0 mg/kg. Terminal half-life of IMM01 range from 53.8 hours to 73.3 hours. The AUC and Cmax of IMM01 show nonlinear increases in the dose range of 0.05 mg/kg to 0.5 mg/kg. Conclusions: Preliminary data from the present phase 1 study of IMM01, a SIRPα IgG 1 fusion protein, demonstrate that IMM01 has an excellent preliminary safety, tolerability and promising anti-tumor activity up to doses of 1.0 mg/kg. Clinical trial information: ChiCTR1900024904.