Study of GDX012 in Patients With MRD Positive AML

A Phase 1, Open Label, Dose Escalation, and Dose Expansion Study to Assess the Safety, Tolerability, and Preliminary Antileukemic Activity of GDX012 in Patients With Minimal Residual Disease (MRD) Positive Acute Myeloid Leukemia

The purpose of this first-in-human study is to assess the safety, tolerability, antileukemic activity and maximum tolerated dose (MTD) of GDX012 in AML patients who are MRD positive by multiparametric flow cytometry.

The study will consist of a dose escalation stage to evaluate various doses of GDX012 after a lymphodepletion regimen comprising fludarabine and cyclophosphamide. Following determination of the MTD of GDX012, the study will expand at the MTD. Patients will be followed up for 12 months, after receiving GDX012.

Inclusion Criteria:

• ≥ 18 years old
• Weight ≥ 40 kg
• Anticipated life expectancy > 3 months prior to lymphodepletion
• Karnofsky Performance Score ≥ 70%
• Histologically confirmed diagnosis of AML
• In complete response (CR) (including CRi/CRp); patients in first, second or subsequent CR (including CRi/CRp) are permitted
• MRD detected in bone marrow by MFC
• Negative pregnancy test (females of childbearing potential only)
• Agree to use effective birth control
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Platelet Count ≥ 20 x 109/L
• Prothrombin Time or INR ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation)
• Partial Thromboplastin Time ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation)
• Hemoglobin ≥ 8.0 g/dL
• Creatinine Clearance ≥ 40mL/min
• Serum Total Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's Syndrome with Direct Bilirubin < 35% of Total Bilirubin)
• ALT ≤ 2.5 x ULN

Exclusion Criteria:

• Cytotoxic chemotherapy within 3 weeks
• Immune therapy within 4 weeks
• Immunosuppressive therapy within 2 weeks (with exceptions)
• Investigational treatment or interventional clinical trial within 4 weeks or 5 half-lives (if known), whichever is longer
• Major surgery within 4 weeks and/or not fully recovered from surgery-related toxicities
• Known hypersensitivity to chemotherapy, other agents, or excipients used in this study
• Female patient that is pregnant or lactating/breastfeeding
• Ongoing toxicity from prior anti-cancer therapy that have not recovered to ≤ Grade 1 (with exceptions)
• History of chronic or recurrent autoimmune or immune-mediated disease requiring steroids or other immunosuppressive treatments (including anti-tumor necrosis factor agents)
• Active CNS involvement (i.e. leukemic infiltration)
• Any other malignancy that requires active therapy
• Uncontrolled intercurrent illness (i.e. acute coronary syndrome in the last 6 months)
• Active infection with HIV, Hepatitis B or Hepatitis C

NOTE: other protocol defined inclusion/exclusion criteria may apply.