Clinical Trial 23710

• Overview

  Study Title:

  A multicenter, open-label, randomized, phase 2 study of venetoclax and azacitidine plus cusatuzumab versus venetoclax and azacitidine alone in newly diagnosed AML patients who are not candidates for intensive therapy

  Summary:

  The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?

  Objective:

  Primary Objective: To determine the efficacy of adding cusatuzumab to venetoclax plus azacitidine (VAC) compared to venetoclax plus azacitidine (VA) alone. Secondary Objectives: To determine the efficacy of adding cusatuzumab to VA compared to VA alone. To determine the efficacy of VAC compared to VA in the adverse, intermediate, and favorable subgroups of participants defined by a newly developed CU VA specific risk stratification model, the ELN 2022 risk model and the risk stratification model published in Bataller et al and Döhner et al. To determine the safety of adding cusatuzumab to VA compared with VA alone. To assess the pharmacokinetics (PK) and immunogenicity of cusatuzumab.

• Treatments

  Therapies:

  BCL-2 inhibitor; Chemotherapy (NOS); Germlined monoclonal antibody (mAb) targeting human CD70

  Medications:

  Azacitidine (5-azacitidine); Cusatuzumab (); GDC-0199 (Venetoclax); Venetoclax ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Men and women ≥18 years old
  • Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study
  • Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19% blasts)
  • Previously untreated AML except may have received emergency leukapheresis, hydroxyurea before study entry to control hyperleukocytosis
  • Deemed unfit for intensive chemotherapy
  • Adequate liver and renal function
  • Women of childbearing potential (WOCBP), defined as fertile women between menarche and post menopause unless permanently sterile, must have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening
  • Must be willing to use contraception as consistent with institutional guidelines regarding the use of contraceptive methods for participants participating in clinical studies

• Exclusion Criteria

  Key Exclusion Criteria:
  • Any prior treatment for AML (except those outlined in inclusion criterion #4) Participant has received a hypomethylating agent (HMA) or venetoclax for MDS or myeloproliferative neoplasm
  • Leukemic involvement in the central nervous system
  • Participants with acute promyelocytic leukemia (APL)
  • ECOG performance status of 4 for participants 18 to 74 years of age and ECOG performance status of 3 or 4 for participants ≥75 years of age
  • Use of immune suppressive agents ≤4 weeks before the first administration of cusatuzumab. Participants may be included if free of systemic corticosteroids >5 days before the first administration of cusatuzumab with the exception of corticosteroids at physiologic replacement doses.
  • Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
  • Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.
  • Any active systemic infection
  • History of prior HSCT (allogeneic or autologous transplants)
  • Congestive hear failure severity that is New York Heart Association Class III or IV
  • Unstable angina
  • Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, or azacitidine or their excipients (e.g., mannitol, an excipient of azacitidine)
  • Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function
  • Any condition for which, in the investigator's opinion, participation would not be in the best interest of the participant (e.g., compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments
  • Major surgery (e.g., requiring general anesthesia) ≤4 weeks prior to initiation of study treatment

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