A Phase 1b Study of CLN-049 in Combination With Azacitidine and Venetoclax in AML Patients

Inclusion criteria

• Patients aged ≥ 18 years of age with newly diagnosed, previously untreated AML (including MDS/AML)
• Patients are not candidates for intensive induction chemotherapy because they are either unfit or otherwise clinically unsuitable for anthracycline/ cytarabine-based induction therapy
• White blood cell (WBC) count at the time of C1D1 ≤ 20,000/μL
• Patients must have previously untreated AML; hydroxyurea for cytoreduction is permitted up to C1D1. Prior therapy for MDS is allowed except for hypomethylating agents and venetoclax.
• Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2
• The patient's laboratory values meet the following criteria:

• Creatinine clearance (CrCl) ≥ 45 mL/min;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN

Exclusion criteria

• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study).
• Diagnosis of acute promyelocytic leukemia or PML:RARA-positive AML.
• Chronic myeloid leukemia in blast phase or AML with BCR:ABL1.
• Mixed phenotype acute leukemia or acute leukemia of ambiguous lineage.
• Active CNS involvement by AML.
• Signs of leukostasis requiring urgent therapy.
• Prior organ allograft, or prior allogeneic hematopoietic stem cell transplant within the last 12 months, or with active graph-versus-host disease.
• Treatment with systemic glucocorticoid therapy or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049.
• Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
• Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications
• Active uncontrolled infection until infection is treated and brought under control.
• Has a history of, or a positive test for human immunodeficiency virus (HIV) 1/2 or primary immunodeficiency disease such as HIV.
• Known history of hepatitis B, hepatitis C (HCV) infection, or acute hepatitis A.
• Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to Grade 1 or less
• History of the following events in conjunction with prior treatment with immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law.
• Live virus vaccines within 28 days of the first dose of CLN-049, during treatment, and until the end of last dose of CLN-049.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds.
• Patient has a history of drug-related anaphylactic reactions to any components of CLN-049, or a history of Grade 4 anaphylactic reaction to any bispecific molecule or monoclonal antibody therapy.
• Known history of prior human anti-human antibody response.