Latest results of a phase 2 study of IMM01 combined with azacitidine (AZA) as the first-line treatment in adults with higher risk myelodysplastic syndromes (MDS).
Authors: Wei Yang, Sujun Gao, Xiaojing Yan, Rong Guo, Lijie Han, Fei Li, Yafei Wang, Junmin Li, Chunkang Chang, Haiping Yang, Ronghua Hu, Hongyan Tong, Xingli Zhao, Qiubai Li, Jingdong Zhang, Xin Du, Zheng Dong, Qiying Lu, Wenzhi Tian, Zhi-Jian Xiao
Journal: Journal of Clinical Oncology (2024)

6510 Background: Patients diagnosed with higher-risk myelodysplastic syndrome (MDS) have poor prognosis. Azacitidine (Aza) has been shown to prolong survival in patients with treatment-naive, higher-risk MDS compared to a menu of standard of care options. IMM01 is a fusion protein comprising a recombinant signal regulatory protein α (SIRPα) and IgG1, exerting anti-tumor effects by inhibiting the "Don't eat me" signal and activating the "Eat me" signal, leading to robust antibody-dependent cellular phagocytosis (ADCP). 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 for patients with untreated higher-risk MDS. Enrolled patients were aged ≥18 years with intermediate to very high risk MDS, as defined by the Revised International Prognostic Scoring System (IPSS-R) score &gt;3.5, and were not eligible for stem cell transplant or intensive chemotherapy. Patients were received intravenous IMM01 at a dosage of 2.0mg/kg/week and subcutaneous AZA at a dosage of 75 mg/m 2 on days1-7 per 28-day cycle. Results: By the cutoff-day of Dec 22, 2023, 57 patients were enrolled in the study. The median age was 64 (30-83) years, with 41 (71.9%) being male, and 55 (96.5%) having an ECOG of ≥1. Based on risk classification per IPSS-R, 43.9% were high risk (HR) and 31.6% were very high risk (vHR). At baseline, the median levels of blood counts were 69 (35-136)g/L for hemoglobin, 43 (2-409)×10 9 /L for platelets and 0.8 (0.1-8.6)×10 9 /L for neutrophils. The median duration of follow-up was 12.8 months (95%CI:9.7-15.3). Among the 51 efficacy evaluable patients, overall response rate (ORR) was 64.7%, including 29.4% complete response (CR) rate, 15.7% marrow CR (mCR) with hematologic improvement (HI), 5.9% HI and 13.7% mCR alone. The median time to response (TTR) was 1.9 months (95%CI:1.8-2.8) and the median duration of response (DoR) was not reached(NR). The median of progression-free survival (PFS) was not reached, with an estimated 12-month PFS of 54.4% (95% CI, 31.4-72.6). NGS analysis identified common mutations in DNMT3A, ASXL1, U2AF1 and RUNX1. Notably, NPM1 mutations significantly correlate with treatment response, particularly achieving CR. The most common ≥G3 treatment related adverse events (TRAEs) (≥10%) included leukopenia (78.9%), thrombocytopenia (66.7%), neutropenia (66.7%), lymphopenia (56.1%), anemia (43.9%), infection (15.8%) and pneumonia (10.5%). Without using of a low priming dose, the Grade ≥3 hemolysis was rare (only 1.8%). Conclusions: IMM01 (without low-dose priming) combined with AZA were well tolerated and showed exciting efficacy results in patients with treatment-naive higher-risk MDS. Clinical trial information: NCT05140811 .