801MO - Efficacy and safety of a phase II study: Timdarpacept (IMM01) combined with azacitidine (AZA) as the first-line treatment in adults with chronic myelomonocytic leukemia (CMML)

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/m² on D1-7 per 28-day cycle.

Results

At the data cut-off on April 1, 2024, 24 patients were enrolled, with a median age of 62 years. Of these, 62.5% were males, and 75.0% had ECOG≥1. Furthermore, 4.2%, 29.2% and 66.7% patients were intermediate risk (IR)-1, IR-2 and high risk (HR) by CPSS-mol classification, respectively. Majority of patients had poor baseline hematologic conditions with a median hemoglobin (Hb) level of 69.5g (32-132)/L and a median PLT count of 73.5 (5-667)×10⁹/L. Among the 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. For those who received initial treatment ≥6months (n=13), the CR rate reached 46.2%. The CR rate of Timdarpacept combined with AZA appears to increase following longer treatment duration. The median time to response (TTR) was 1.8 months and the median duration of response (DoR) was 14.1months. The median duration of CR was 10.8 months. Median OS was not reached, with an estimated 12-month OS of 66.7%. 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 the use of a low dose priming regimen, only 4.2% Grade ≥3 hemolysis occurred.

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 exciting efficacy results for patients with treatment-naive CMML-1 and -2.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

Funding

ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

Disclosure

Z. Dong, Z. Wang, Q. Lu, W. Tian: Financial Interests, Personal, Full or part-time Employment: ImmuneOnco Biopharmaceuticals (Shanghai) Inc. All other authors have declared no conflicts of interest.