A First-in-Human Phase I Dose Escalation Study of IMM01, Sirpα Fc Protein in Patients with Relapsed or Refractory Lymphoma

Background: IMM01 is a recombinant human signal regulatory protein α (SIRPα) IgG 1 fusion protein that exerts dual-mechanism antitumor activity via enhancing tumor cell phagocytosis and stimulating T-cell anti-tumor responses by binding and blocking CD47 on tumor cell membrane. Based on preclinical data, IMM01 shows unique property of weak human erythrocyte conjugation so that severe hemolysis is not expected in the clinic. We report the results of the IMM01 dose escalation study in patients with relapsed or refractory (R/R) lymphoma.

Methods: This study was a first-in-human, phase I, dose escalation study to evaluate the preliminary safety and efficacy of IMM01. Patients with R/R lymphoma were enrolled in this study. An accelerated titration followed by a 3+3 design was used to assess the safety and tolerability of IMM01 monotherapy at 8 planned dose levels ranging from 0.003mg/kg to 2.0mg/kg. IMM01 was administered intravenously once weekly for 4 weeks followed by 1 week rest in a 5-week cycle. Primary endpoints were to evaluate the safety and tolerability of IMM01. Pharmacokinetics, pharmacodynamics and anti-tumor activity based on Lugano criteria were also assessed.

Results: As of December 31, 2021, 29 patients (17 males, 12 females) of R/R lymphoma were enrolled to 8 ascending dose cohorts as planned, including 7 Hodgkin Lymphoma (HL), 13 Follicular Lymphoma (FL), 4 Diffuse Large B cell Lymphoma (DLBCL), 4 Angioimmunoblastic T-Cell Lymphoma (AITL) and 1 Marginal Zone B-cell Lymphoma (MZL). The median age was 49 years old (range: 19-75).

Among 29 patients treated, only one DLT of Grade 4 PLT decreased occurred (one at the dose level of 1.5mg/kg). The MTD was not reached up to 2.0mg/kg of IMM01. The most common TRAEs (occurring in ≥30% of patients) included anti-erythrocyte antibody positive (58.6%, n=17), haemolysis (51.7%, n=15), white blood cell count decreased (51.7%, n=15), infusion related reaction (IRR) (51.7%, n=15), platelet count decreased (44.8%, n=13), hypercholesterolaemia (44.8%, n=13), neutrophil count increased (41.4%, n=12), neutrophil count decreased (41.4%, n=12), anemia (41.4%, n=12). The most common Grade ≥3 TRAEs observed on study (occurring in ≥5% of patients) included anemia (13.8%, n=4), platelet count decreased (10.3%, n=3), and white blood cell count decreased (6.9%, n=2). No patient experienced G4/5 TRAEs except for the one with the DLT event of G4 platelet count decreased. 15 patients (51.7%) had infusion related reaction (IRR) across dose levels, all of which were G1/2. PLT decrease did not appear dose-dependent mode and no serious bleeding occurred. No hemagglutination was reported. No treatment-related SAE was reported. No patient discontinued the study due to AEs except for the patient with DLT who occurred G4 PLT decrease.

In 26 response evaluable patients, one patient with FL achieved CR at 0.01 mg/kg. Two patients (1 cHL at 0.15mg/kg and 1 AITL at 2.0mg/kg) achieved PR. Disease control rate (DCR) was 57.7% (15/26). The cHL patient who achieved PR is continuing to receive IMM01 treatment and DOR has been more than 20 months. The AUC and C_max of IMM01 showed nonlinear increases at all the dose levels. The average half-life is 1.42~2.86 days.

Conclusions: IMM01 up to 2.0mg/kg dose level was generally well-tolerated and single-agent activity was seen in patients with R/R Lymphoma. IMM01 does not require a lower 'priming' dose to prevent anemia. The study is currently expanding at both 1.5 and 2.0mg/kg in multiple lymphoma indications to further assess safety and efficacy in relation to doses.

No relevant conflicts of interest to declare.