Updated results of a phase 2 study: Timdarpacept (IMM01) combined with azacitidine (AZA) as the first-line treatment in adults with chronic myelomonocytic leukemia (CMML).

6577 Background: Timdarpacept 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). Methods: The study (NCT05140811) assessed the safety and efficacy of Timdarpacept combined with AZA as first-line treatment for newly diagnosed CMML patients. Timdarpacept was administered intravenously at a dosage of 2.0mg/kg/week, while subcutaneous AZA was given at a dosage of 75 mg/m 2 on D1-7 per 28-day cycle. Results: At the cut-off date on Dec 31, 2024, 24 patients, with a median age of 62, males 62.5%, and 75.0% ECOG≥1, were enrolled. 33.3% and 66.7% patients were and high risk (HR), respectively. Majority of patients had poor baseline of hematologic conditions with a median hemoglobin (Hb) level of 69.5 (32-132) g/L and a median platelet (PLT) count of 73.5 (5-667)×10 9 /L. The median duration of follow-up was 21.0 months (95%CI, 19.3-23.3). Among 22 efficacy evaluable patients, overall response rate (ORR) was 72.7%, including 27.3% complete response (CR), 13.6% marrow CR (mCR) with hematologic improvement (HI), 4.5% HI and 27.3% mCR alone. The median time to response (TTR) was 1.8 months and the median duration of response (DoR) was 16.9 months (95%Cl, 5.1-not reached [NR]). The median time to CR (TTCR) was 3.7 months and the median duration of CR (DoCR) was 13.6 months (95%Cl, 5.7-NR). The median of progression-free survival (PFS) was 17.8 months (95%Cl, 5.3-NR), with an estimated 12-month PFS of 59.0% (95%Cl, 33.4-77.6). Median OS has not been reached yet. The most common ≥Grade 3 TRAEs (≥10%) included lymphopenia (66.7%), leukopenia (62.5%), neutropenia (58.3%), thrombocytopenia (50.0%), anemia (29.2%) and pneumonia (16.7%). Without using of a low dose priming regimen, Grade ≥3 hemolysis occurred in 1 patient (4.2%). Conclusions: Timdarpacept, without a low-dose priming, combined with AZA, was well tolerated in 1L CMML. The combination, when compared to the historical data of AZA monotherapy, showed promising efficacy results for patients with treatment-naive CMML-1 and -2. Clinical trial information: NCT05140811 .