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

Prior treatment

• Patients willing and able to receive standard intensive chemotherapy.
• 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 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
• 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.
• Known history of prior human anti-human antibody response.

Other illness

• 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.
• 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.

Lab values

• 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.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds.

Other

• 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.

• Patients aged ≥ 18 years of age with newly diagnosed, previously untreated AML (including MDS/AML)
  • De novo and secondary AML are eligible
  • Patients with molecularly defined AML subtypes (including but not limited to FLT3-mutated, IDH1/2-mutated, NPM1-mutated, KMT2A rearranged, and TP53-mutated AML) are eligible
  • Patients with TP53-mutated AML are eligible
• White blood cell (WBC) count at the time of C1D1 ≤ 20,000/μL
• Patients must have previously untreated AML; No prior AML treatment other than hydroxyurea for cytoreduction and one dose of intrathecal chemotherapy for suspected central nervous system (CNS) involvement (that is ruled out) is allowed. 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