PDR001-X2105: This is a phase I trial assessing the safety and tolerability of using immunotherapy drugs (PDR001 and /or MBG453) in combination with chemotherapy (Decitabine) to treat patients with Acute Myleoid Leukaemia or High Risk Myelodysplastic SyndromePhase 1b, Multi-arm, Open-label Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Inclusion

1. Written informed consent must be obtained prior to any screening procedures

2. Male or female patients ≥ 18 years of age who present with one of the following:

   Arms 1-3:

   • Relapsed/refractory AML following ≥1 prior therapies who have relapsed or exhibited refractory disease (primary failure) and are deemed by the investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established chemotherapy regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
   • Newly diagnosed AML patients who are suitable for treatment with decitabine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
   • Intermediate or high risk MDS or MDS/MPN including CMML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)

   Arms 4-5:

   • Refractory / relapsed AML following ≥1 prior therapies (Arms 4a & 5a)
   • Intermediate or high risk MDS or MDS/MPN including CMML who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note: hypomethylating agent failure is defined as progressive disease on hypomethylating agent therapy or lack of clinically meaningful response as deemed by investigator after at least 4 cycles of hypomethylating agent therapy.)

   Arm 6:

   • Newly diagnosed AML patients who are suitable for treatment with azacitidine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6a)
   • Intermediate or high-risk MDS or MDS/MPN including CMML (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6b)
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and be willing to undergo a bone marrow aspirate and/biopsy at screening, during and at the end of therapy on this study. Exceptions may be considered after documented discussion with Novartis.
5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by the investigator and as per local decitabine package insert.
6. Arm 6: Patients must be fit for standard treatment with azacitidine as determined by the investigator and as per the local azacitidine package insert.