617O - Lemzoparlimab, a differentiated anti-CD47 monoclonal antibody, in combination with azacitidine (AZA) in patients with newly diagnosed higher risk myelodysplastic syndrome (HR-MDS): Initial clinical results

Background

Lemzoparlimab (TJ011133) is a differentiated CD47 antibody targeting a distinct epitope to enable a unique red blood cell sparing property while retaining strong anti-tumor activity. We report initial data in an ongoing phase 2 trial in HR-MDS (NCT04202003).

Methods

Patients with untreated IPSS-R intermediate or high-risk MDS, received lemzoparlimab at 30 mg/kg IV weekly and AZA at 75 mg/m² SC on Days 1–7 in a 28-day cycle. Efficacy was assessed by IWG 2006 criteria per investigator.

Results

As of March 31, 2022, 53 patients were enrolled and baseline characteristics includes median age of 65 years (range, 40-80), 74% male, 91% ECOG≤1, 87% MDS with excess blasts according to WHO classification, 59%/9%/32% with good, intermediate, and poor/very poor cytogenetic risk. The patients had aberrant baseline hematologic conditions with decreased median levels of hemoglobin (G3) 71 g/L, platelet (G3) 43×10⁹/L and neutrophil (G2) 1.1×10⁹/L, respectively. Common Grade 3/4 treatment-related AEs (TRAEs) occurring in ≥20% pts included decreased platelet count (60%), decreased neutrophil count (53%), decreased WBC count (53%) and anemia (40%). One patient had Grade 5 pneumonia TRAE. These hematologic changes were commonly observed in MDS patients treated with AZA monotherapy in China (Du 2018). Among the 29 efficacy evaluable patients who received initial treatment ≥ 4 mo, overall response rate (ORR) was 86.2%, with 31% complete response (CR) rate, 10% hematologic improvement (HI) alone, 44.8% marrow CR (5/13 also with HI), and a median treatment duration of 4.6 mo (range, 1.8-10.5). Among the 15 efficacy evaluable patients who received initial treatment ≥ 6 mo, CR rate was 40%. Most CR patients showed reduction in VAF of MDS-related gene mutation and MRD negativity (≤10^-4) by flow cytometry. Biomarker analyses suggest potential correlation of certain gene mutation or bone marrow immunophenotyping with clinical response.

Conclusions

Without a priming dose of lemzoparlimab, combination treatment with AZA is well tolerated and showed clinically meaningful efficacy results in newly diagnosed HR-MDS. A randomized phase 3 MDS trial is planned.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

I-Mab biopharma.

Funding

I-Mab biopharma.

Disclosure

All authors have declared no conflicts of interest.