Timdarpacept (IMM01) combined with azacitidine (AZA) as first-line therapy in adults with higher risk chronic myelomonocytic leukemia (CMML): results from a prospective, multicenter, phase II study

Timdarpacept (IMM01) is a recombinant signal regulatory protein α–IgG1 fusion protein that exerts antitumor activity by blocking the “don’t eat me” signal while simultaneously activating the “eat me” signal, inducing robust antibody-dependent cellular phagocytosis. We report the final phase II results of treatment-naïve higher risk chronic myelomonocytic leukemia (CMML) patients treated with IMM01 in combination with azacitidine. We assessed the safety and efficacy of IMM01 in combination with azacitidine (AZA) as first-line therapy for newly diagnosed CMML patients. IMM01 was administered intravenously at 2.0 mg/kg weekly, and AZA was administered subcutaneously at 75 mg/m² on days 1–7 of each 28-day cycle. As of the data cut-off on May 13, 2025, 24 patients were enrolled. Of 22 efficacy-evaluable patients, the overall response rate (ORR) was 72.7% (16/22; 95% CI 49.8–89.3), including 27.3% complete response (CR), 13.6% marrow CR (mCR) with hematologic improvement (HI), 4.5% HI alone, and 27.3% mCR alone. The median time to response was 1.8 months (range, 0.9–3.6), and the median duration of response was 16.9 months (95% CI 5.1–NE). Median overall survival and progression-free survival were 22.2 months (95% CI 9.0–NE) and 17.8 months (95% CI 5.3–NE), respectively. The most common grade ≥ 3 treatment-related adverse events (≥ 10%) were lymphopenia (66.7%), leukopenia (62.5%), neutropenia (62.5%), thrombocytopenia (58.3%), anemia (33.3%), and pneumonia (16.7%). IMM01 in combination with AZA was generally well tolerated and effective in treatment-naïve higher risk CMML patients. Trial registration ClinicalTrials.gov identifier: NCT05140811.