PBSS1113 in Combination With Azacitidine to Treat Patients With AML/MDS

Inclusion criteria

• 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.

Exclusion criteria

• Leukemia Subtypes: Diagnosis of acute promyelocytic leukemia (APL), classified as AML-M3 per the French-American-British (FAB) criteria or APL with PML-RARA fusion gene per standard diagnostic classifications.
• Concomitant Malignancies: Diagnosis of another active malignant tumor within the screening period, except for the target AML or MDS indications (as evaluated by the investigator).
• Hyperleukocytosis: White blood cell (WBC) count > 25 × 10⁹/L during screening. Note: Hydroxyurea use is permitted to stabilize the WBC count below this threshold prior to first dose.
• Contraception: Female patients of childbearing potential, male patients, and their partners who are unwilling to practice a medically accepted, highly effective method of contraception during the treatment period and for at least 6 months following the final dose of the investigational drug. Note: Women are considered postmenopausal if they have experienced at least 12 consecutive months of amenorrhea with no alternative pathological cause.
• Prior/Concomitant Therapies:
• Received radiotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, traditional Chinese medicine indicated for oncology, chemotherapy, or any other investigational agent within 14 days prior to the first dose of the study drug.
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) with evidence of active graft-versus-host disease (GVHD), or requiring systemic immunosuppressive therapy for GVHD.
• Use of strong CYP3A inhibitors or inducers within 14 days prior to the first dose of the study drug (unless on a stable, clinically justified regimen approved by the investigator).
• Residual Toxicity: Unresolved toxicities from prior anti-cancer therapies that have not recovered to ≤ Grade 1 per CTCAE v5.0 (excluding alopecia and stable Grade 2 peripheral neuropathy, if applicable).
• Surgery: Major surgical procedures or significant traumatic injuries within 28 days prior to the first dose of the study drug, or an anticipated requirement for major surgery during the trial.
• Gastrointestinal Disorders: Difficulty swallowing or any clinically significant gastrointestinal disease or malabsorption syndrome that would significantly impair the oral absorption of the investigational drug.
• Infections and Comorbidities:
• Active, clinically significant, or poorly controlled fungal, bacterial, or viral infections at baseline.
• Known human immunodeficiency virus (HIV) infection (anti-HIV positive).
• Active hepatitis B virus (HBV; HBsAg positive and HBV DNA ≥ 2000 copies/mL or ≥ 500 IU/mL) or active hepatitis C virus (HCV; HCV antibody positive and HCV RNA positive).
• Active syphilis infection.
• Any severe, poorly controlled systemic comorbidities (e.g., unstable psychiatric, neurological, cardiovascular, respiratory, hepatic, or renal diseases).
• Hypersensitivity: Known hypersensitivity or allergy to the investigational drug (PBSS1113), azacitidine, or any of their excipients.
• Investigator Discretion: Any other clinical condition or social circumstance that, in the opinion of the investigator, would compromise patient safety or interfere with the scientific integrity of the study data.