Study of Azacitidine in Combination With Pembrolizumab in R/R AML Patients and in Newly Diagnosed Older Patients

Inclusion Criteria

Cohort #1

• Have histologically or cytologically confirmed relapsed or refractory AML (i.e. ≥5% blasts by manual differential on bone marrow aspirate/biopsy/flow cytometry), excluding acute promyelocytic leukemia (APL; FAB M3; t(15;17))
• Be willing and able to provide written informed consent/assent for the trial.
• Be > 18 years of age on day of signing informed consent.
• Not be appropriate candidate for intensive salvage chemotherapy due to co-morbidities or other disease- or treatment-related factors.

NOTE: Subjects who received prior treatment with hypomethylating agents either for Myelodysplastic Syndrome (MDS), Myeloproliferative Neoplasm (MPN), or AML will be eligible if they achieved response to hypomethylating agents in the past (PR or CR) and did not progress while receiving therapy with hypomethylating agents.

NOTE: Subjects who had prior allogeneic stem cell transplant (alloHSCT) will be eligible as long as they have been at least 3 months after allogeneic HSCT and are off of all immune suppression for at least 3 weeks (>21 days) and have no evidence of active graft versus host disease (GVHD). Subjects with prior alloHSCT will NOT be eligible for enrollment during the safety run in phase.

• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
• ECOG performance status ≤ 2.
• A projected life expectancy of at least 12 weeks.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.8.2) must be willing to use an adequate method of contraception as outlined in Section 5.8.2 - Contraception, for the 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 preferred contraception for the subject.

• Male subjects of childbearing potential (Section 5.8.2) must agree to use an adequate method of contraception as outlined in Section 5.8.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.

Cohort #2

• Have histologically and cytologically confirmed newly diagnosed AML (i.e. ≥ 20% blasts by manual differential on bone marrow aspirate/biopsy and/or in peripheral blood), excluding acute promyelocytic leukemia (APL; FAB M3, t (15;17))
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥65 years of age on day of signing informed consent.
• Have received NO prior treatment for AML with the exception of hydroxyurea/leukapheresis.

NOTE: Subjects may have been treated for pre-existent myeloid disorder such as Myelodysplastic Syndrome or Myeloproliferative Neoplasm excluding hypomethylating agents.

• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
• ECOG performance status ≤ 2.
• A projected life expectancy of at least 12 weeks.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.8.2) must be willing to use an adequate method of contraception as outlined in Section 5.8.2 - Contraception, for the course of the study through 120