All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
To characterize the safety and tolerability of 1) MBG453 as a single agent or in combination with PDR001 or 2) PDR001 and/or MBG453 in combination with decitabine in AML and high risk MDS patients, and to identify recommended doses for future studies.
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Jul 06, 2017
Nov 01, 2021
18 Years and older (Adult, Older Adult)
Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.
PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2.
MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer).
Written informed consent must be obtained prior to any screening procedures
Male or female patients ≥ 18 years of age who present with one of the following:
Refractory/relapsed AML following ≥1 prior therapies 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)
De novo 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)
High risk MDS (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
Refractory / relapsed AML following ≥1 prior therapies (Arms 4a & 5a)
High risk MDS 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.)
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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.
Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by the investigator and as per local decitabine package insert.