A Phase Ib/II, Open-Label, Dose-Escalation and Cohort Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PBSS1113 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are highly heterogeneous myeloid malignancies where few effective targeted therapies are available. While venetoclax has significantly advanced the treatment landscape, therapeutic resistance remains a critical challenge. Consequently, patients with relapsed or refractory (R/R) AML/MDS face a profound unmet medical need for novel therapeutic options. PBSS1113 has demonstrated robust anti-leukemic activity in both in vitro and in vivo models, alongside an acceptable safety profile in a Phase I study. This Phase Ib/II trial will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of PBSS1113 in combination with azacitidine for treatment-naive unfit AML, R/R AML, and higher-risk MDS populations.
• Age and Gender: Age ≥ 18 years at the time of signing the informed consent form, male or female.
• Disease Status: Must meet one of the following diagnostic criteria:
• Relapsed or refractory (R/R) acute myeloid leukemia (AML).
• Newly diagnosed AML in patients who are ineligible for intensive induction chemotherapy (including primary AML or secondary AML arising from myelodysplastic syndromes \[MDS\]).
• Higher-risk MDS, defined per the Revised International Prognostic Scoring System (IPSS-R) as Intermediate risk (score \> 3.5 points), High risk, or Very High risk. Prior therapy with hypomethylating agents (HMAs, e.g., decitabine or azacitidine) is permitted.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Life Expectancy: Expected survival period ≥ 3 months.
• Organ Function: Baseline organ function meeting the following laboratory criteria:
• Hepatic: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN.
• Renal: Serum creatinine ≤ 1.5 × ULN.
• Coagulation: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) ≤ 1.5 × ULN; International Normalized Ratio (INR) ≤ 1.5 × ULN.
• Cardiac: Fridericia-corrected QT interval (QTcF) \< 450 ms for males and \< 470 ms for females.
• Compliance: Able and willing to adhere to the study procedures, scheduling, and follow-up examinations outlined in the protocol.
• Informed Consent: Capable of understanding and voluntarily providing written informed consent prior to the initiation of any trial-specific screening procedures.