Background: Acute myeloid leukemia (AML) is the most common acute form of leukemia in adults and has an aggressive disease course. Investigational agent TQB3909, a novel, highly selective BCL-2 inhibitor, was shown in preclinical findings to synergistically induce apoptosis in myeloid malignancies. Here, we present follow up safety and efficacy data from a phase 1b/2 study evaluating TQB3909 + azacitidine (AZA) in adults with AML.

Aims: We present safety and efficacy results from ongoing TQB3909-Ib/II-03 (NCT07011186). The primary and key secondary endpoints were safety per CTCAE V5.0 and response rate per the 2017 European Leukemia Net (ELN) response criteria for AML.

Methods Elderly (≥65 years)/unfit treatment-naive (TN) and relapsed or refractory (R/R) AML (≥18 years) patients (pts) were enrolled. TQB3909 (200，400 and 600 mg) was administered orally once daily in repeated 28-day cycles, and azacitidine (75mg/m2 for 7 days/cycles) was administered subcutaneously or intravenously. A daily ramp-up schedule for TQB3909 was used to mitigate potential risk of tumor lysis syndromes (TLS). Pts received treatment of TQB3909 and azacitidine until disease progression, intolerable toxicity, death, or any other reasons for termination.

Results As of June 17, 2025, 62 pts were enrolled，including 56 pts with AML (R/R[n= 9]; elderly/unfit TN[n=47]). The median age was 68(range, 62 to 73) years and 31% of pts were male. All patients treated with TQB3909+AZA reported TEAEs，with 91.07% Grade 3/4 AEs; and 53.57% SAEs. Common TEAEs (≥30%) included white blood cell count decreased (76.79%), neutropenia (75%), thrombocytopenia (75%), hypokalemia (50%), diarrhea (39.29%), anemia (37.5%), pyrexia (30.36%). Grade ≥3 TEAEs reported in ≥10% of pts were white blood cell count decreased (75%), neutropenia (73.21%),thrombocytopenia (66.07%),anemia (33.93%),pneumonia (17.86%),hypokalemia (17.86%), febrile neutropenia (14.29%) and sepsis (12.5%). No TLS was reported.

In patients with TN AML treated with TQB3909+AZA, the overall response (ORR=CR+CR with incomplete hematologic recovery [CRi]+morphologic leukemia-free state [MLFS]+PR) and composite complete remission (CRc=CR+CRi) rates were 83.8% and 67.6%, respectively. The median follow-up was 5.26 months (95% confidence interval [CI], 4.44 to 7.1), the median overall survival (OS) was 10.6 months (95% CI, 5.16 to NR). The median time to first CRc (mTTCRc) response was 0.95 months (95% CI, 0.92 to 1.97). The median duration of CRc was not reached (95% CI, 3.91 to NR). In the 400mg cohort (n=25), ORR and CRc were 88% and 76%, respectively; mTTCRc was 0.95 months ((95% CI, 0.92 to 1.38); the median duration of CRc was not reached (95% CI, 2.86 to NR); median OS was not reached (95% CI, 3.19 to NR). Among 9 pts with R/R AML treated with TQB3909+AZA, ORR and CRc were 75% and 62.5%, respectively.

Conclusions This new BCL-2 inhibitor TQB3909 combined with AZA demonstrated significant efficacy in pts with elderly/unfit TN and R/R AML. No significant new safety findings were observed.

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2025
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