MRD-guided Treatment in NPM1mut AML Patients

Inclusion Criteria:

• Signed informed consent

• Age ≥18 years

• Patients with NPM1mut AML in complete morphologic remission after conventionalchemotherapy (anthracycline ± cytarabine based)

• Detectable measurable residual disease (MRD) indicating imminent hematologicalrelapse (NPM1mut MRD ratio >1%, confirmed by central lab)

• Patients who are not eligible for immediate allogeneic hematopoietic stem celltransplantation

• Patients who are not eligible to undergo alternative intensive treatment

• Intended AZA therapy for molecular relapse

• Eastern cooperative oncology Group (ECOG) performance status of 0 or 1

• Demonstrate adequate organ function as defined by protocol, all labs should beperformed within the screening period.

• Negative pregnancy test in women of childbearing potential (negative urine or serumpregnancy within 3 days prior to receiving study treatment). If the urine test ispositive or cannot be confirmed as negative, a serum pregnancy test will berequired.

• Female subjects of childbearing potential (Section 5.9.2) must be willing to use anadequate method of contraception as outlined in Section 5.9.2 - Contraception, forthe course of the study through 120 days after the last dose of study medication.Note: Abstinence is acceptable if this is the usual lifestyle and preferredcontraception for the subject.

• Male subjects with procreative capacity (Section 5.9.2) must agree to use anadequate method of contraception as outlined in Section 5.9.2- Contraception,starting with the first dose of study therapy through 120 days after the last doseof study therapy. Note: Abstinence is acceptable if this is the usual lifestyle andpreferred contraception for the subject.

Exclusion Criteria:

• Prior allogeneic hematopoietic stem cell transplantation

• Treatment with any investigational drug within 4 weeks to study therapy or less than 5 half-lives preceding the first dose of trial medication, whichever is longer.

• Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or norecovering (i.e., ≤ Grade 1 or at baseline) from adverse events due to agentsadministered more than 4 weeks earlier.

• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2weeks prior to study day 1 or no recovering (i.e., ≤ Grade 1 or at baseline) fromadverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2neuropathy are an exception to this criterion and may qualify for the study. Note:If subject received major surgery, they must have recovered adequately from thetoxicity and/or complications from the intervention prior to starting therapy.

• Prior treatment with an anti-programmed cell death protein (anti PD-1, anti PD-L1 oranti PD-L2 agent).

• Known hypersensitivity to any of the drugs within this study, their constituents orto drugs with similar chemical structure.

• Receiving immunosuppressive therapy within 7 days prior to the first dose of trialmedication.

• Known history of active Bacillus Tuberculosis (TB).

• Known additional malignancy that is progressing or requires active treatment.Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma ofthe skin that has undergone potentially curative therapy or in situ cervical cancer.

• Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Subjects with previously treated brain metastases may participateprovided they are stable (without evidence of progression by imaging for at leastfour weeks prior to the first dose of trial treatment and any neurologic symptomshave returned to baseline), have no evidence of new or enlarging brain metastases,and are not using steroids for at least 7 days prior to trial treatment. Thisexception does not include carcinomatous meningitis which is excluded regardless ofclinical stability.

• Autoimmune disease that has required systemic treatment in the past 2 years (i.e.with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

• Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considereda form of systemic treatment.

• Known history of, or any evidence of active, non-infectious pneumonitis.

• Liver cirrhosis or malignant liver tumor.

• Known severe congestive heart failure, incidence of clinically unstable cardiac orpulmonary disease.

• Active infection requiring systemic therapy.

• History or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the trial, interfere with the subject'sparticipation for the full duration of the trial, or is not in the best interest ofthe subject to participate, in the opinion of the treating investigator.

• Known psychiatric or substance abuse disorders that would interfere with cooperationwith the requirements of the trial.

• Pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visitthrough 120 days after the last dose of trial treatment

• Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis Cvirus (HCV) RNA [qualitative] is detected).

• Live vaccine within 30 days of planned start of study therapy. Note: Seasonalinfluenza vaccines for injection are generally inactivated flu vaccines and areallowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuatedvaccines, and are not allowed.