Preliminary Results of a Phase 2 Study of IMM01 Combined with Azacitidine (AZA) As the First-Line Treatment in Adult Patients with Chronic Myelomonocytic Leukemia (CMML)

Background:

Patients with Chronic Myelomonocytic Leukemia (CMML) have poor prognosis and an inherent risk for transformation to acute myeloid leukemia. IMM01 is a recombinant signal regulatory protein α (SIRPα) IgG1 fusion protein that exerts anti-tumor activity via blocking “Don't eat me” signal and activating the "Eat me" signal to induce strong antibody-dependent cellular phagocytosis (ADCP). Furthermore, IMM01 activated macrophages could process and present tumor antigen to T cells and elicit long-last tumor-specific T cell immune response.

Methods:

This is an open-label, multi-center, phase 2 study (NCT05140811) that evaluated safety and efficacy of IMM01 in combination with AZA as the first-line treatment in patients with newly diagnosed CMML. We enrolled patients aged 18 years or older with the diagnosis of CMML, including subtypes CMML-1 and 2, not eligible for stem cell transplant. Patients with treatment-naive CMML were administered intravenous IMM01 at a dosage of 2.0mg/kg/week and subcutaneous AZA at a dosage of 75 mg/m² on D1-7 per 28-day cycle. Safety was assessed by CTCAE V5.0 and efficacy by IWG 2006 (MDS) criteria.

Results:

Between August 4, 2022 and July 7, 2023, 24 patients were enrolled: median age was 62 years, 15 (62.5%) males, 18(75.0%) ECOG≥1. Additionally, 1(4.2%), 7(29.2%) and 16(66.7%) patients were intermediate risk(IR)-1, IR-2 and high risk(HR) by CPSS-mol classification, respectively. According to World Health Organization (WHO) classification of CMML, patients enrolled included CMML-1(50.0%) and CMML-2(50.0%). Majority of patients had poor baseline hematologic conditions with a median Hb of 69.5 (32, 132) g/L and a median PLT of 73.5 (5, 667)×10⁹/L. By the data cut-off date of July 7, 2023, the median follow-up for the study was 4 months (95%CI:3.3-4.8). Among the 16 efficacy evaluable patients who received initial treatment ≥3 months, overall response rate (ORR) was 87.5% (14/16), including 25.0% (4/16) complete response (CR), 18.8% (3/16) marrow CR (mCR) with hematologic improvement (HI), 6.3% (1/16) HI and 37.5% (6/16) mCR alone. Among the 9 efficacy evaluable patients who received initial treatment ≥4 months, ORR was 88.9% (8/9), including 44.4% (4/9) CR, 11.1% (1/9) mCR with HI and 33.3% (3/9) mCR alone. The CR rate of IMM01 combined with AZA is increasing with longer treatment duration. The median duration of response (DoR) was not reached. NGS analysis of bone marrow collected from responders were included in this study. The most frequent treatment related adverse events (TRAEs) (≥20%) were lymphopenia (70.8%), leukopenia (70.8%), neutropenia (70.8%), thrombocytopenia (58.3%), infusion related reaction (33.3%), anemia (25.0%), pyrexia (25.0%), pneumonia (25.0%), constipation (20.8%), nausea (20.8%), vomiting (20.8%) and leukocytosis (20.8%). The most common ≥Grade 3 TRAEs (≥10%) included lymphopenia (66.7%), neutropenia (54.2%), leukopenia (54.2%), thrombocytopenia (54.2%), anemia (20.8%) and pneumonia (16.7%), all of which were commonly reported in AZA monotherapy studies for treatment naive MDS/CMML patients in China. The study is ongoing.

Conclusions:

Preliminary data showed that IMM01 (without a low-dose priming) combined with AZA were well tolerated. The combo, when compared to the historical data of AZA alone, showed exciting efficacy result for patients with treatment-naive CMML1-2.