A Study to Assess Adverse Events and Change in Disease Activity When Intravenous (IV) Pivekimab Sunirine is Given in Combination With Oral Venetoclax and IV or Subcutaneous Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML)

Korábbi kezelés

• Participants must not have received a hypomethylating agent, any BCL-2 inhibitors including venetoclax, and/or chemotherapeutic agent for Myelodysplastic syndromes (MDS) or AML, CAR-T cell therapy, be currently participating in another clinical study, received any investigational treatment within 30 days prior to the first use of study combination product.
• Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study and for approximately 7 months after the last dose of any study drug. Female participant of childbearing potential must agree to use at least 1 protocol specified method of birth control and male participant, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.

Más betegség

• Known active central nervous system (CNS) involvement with AML. Participants may have non-CNS extramedullary disease (excludes participants with myeloid sarcoma as the only disease manifestation at screening).
• Participants with history of any malignancies within 2 years prior to screening with exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of the breast, in situ - carcinomas of bladder and esophagus; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, and previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and have no evidence of relapse within 2 years.

Egyéb

• Acute promyelocytic leukemia (APL), blast phase of CML or AML with t(9;22) or BCR:ABL1 fusion, transformation from myeloproliferative neoplasm (MPN), Chronic Myelomonocytic Leukemia (CMML), myelodysplastic/myeloproliferative neoplasm unspecified, or myeloid sarcoma.

• Participants must have newly diagnosed, untreated confirmed acute myeloid leukemia (AML) diagnosis as per the 5th edition of World Health Organization (WHO) criteria with a projected life expectancy of at least 12 weeks.
• CD123-positive
• Ineligible for intensive induction therapy (chemotherapy) defined by:
  • ≥ 75 years of age OR
  • ≥ 18 to 74 years of age with at least one of the following co-morbidities:
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
  • Cardiac history of congestive heart failure requiring treatment or ejection fraction ≤ 50% or chronic stable angina
  • Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
  • Creatinine clearance ≥ 30 mL/min to < 45 mL/min
  • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × upper limit of normal (ULN)
  • Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the medical monitor before study enrollment.
• ECOG performance status 0 to 2 for subjects ≥ 75 years of age or 0 to 3 for subjects ≥ 18 to 74 years of age.
• White blood cell (WBC) count < 25 × 10\^9/L (hydroxyurea is permitted prior to beginning study treatment to reduce the WBC count to < 25 × 10\^9/L).
• Subjects must have adequate organ function:
  • Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
  • Adequate liver function as demonstrated by:
  • Aspartate aminotransferase (AST) ≤ 3.0 × ULN*,
  • Alanine aminotransferase (ALT) ≤ 3.0 × ULN*,
  • ---*Unless considered due to leukemic organ involvement
  • Subjects < 75 years of age may have total bilirubin ≤ 3 x ULN
  • Subjects ≥ 75 years of age total bilirubin ≤ 1.5 × ULN unless elevated level is considered to be due to Gilbert's syndrome or hemolysis, total bilirubin must be < 3 x ULN and direct bilirubin < 1 x ULN
  • Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × ULN International Normalized Ratio (INR) <1.5