Main Inclusion Criteria:

          -  Male or female patients ≥ 18 years of age at the date of ICF signature who present
             with one of the following:

               1. Relapsed/refractory AML following ≥1 prior therapies (but ≤3 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)

               2. First line AML patient unfit for standard induction chemotherapy (includes both
                  de novo and secondary AML), except in countries where approved therapies are
                  available. Patients who are suitable for hematopoietic stem cell transplantation
                  and willing to receive it are excluded.

               3. High-risk MDS patient (high and very high-risk groups according to rIPSS) who
                  have failed hypomethylating agent therapy.

          -  ECOG performance status ≤ 1

          -  TP53wt tumor. At minimum exons 5, 6, 7 and 8 in the TP53 gene must be sequenced and
             determined to contain no mutations. The TP53 status must be obtained from a
             bone-marrow sample, collected no longer than 3 months before signing the main ICF.

          -  Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to
             the institutional guidelines and be willing to undergo a bone marrow aspirate and/or
             biopsy at screening, during and at the end of therapy on this study. Exceptions may be
             considered after documented discussion with Novartis.

        Main Exclusion Criteria:

        Patients eligible for this study must not meet any of the following criteria:

          -  Prior combination treatment with compounds having the same mode of action:

               -  mdm2 or mdm4 inhibitors combined with TIM-3 inhibitors (for patients enrolled in
                  treatment arm1)

               -  mdm2 or mdm4 inhibitors combined with Bcl-2 inhibitor (for patients enrolled in
                  treatment arm2)

          -  History of severe hypersensitivity reactions to any ingredient of study drug(s) and
             other monoclonal antibodies (mAbs) and/or their excipients.

          -  Patients with acute promyelocytic leukemia with PML-RARA.

          -  Allogeneic stem cell transplant (HSCT) within last 6 months and/or active GvHD
             requiring systemic immunosuppressive therapy.

          -  GI disorders impacting absorption of oral HDM201 or venetoclax.

          -  Evidence of active bleeding or bleeding diathesis or major coagulopathy (including
             familial).

          -  Patients with active, known or suspected autoimmune disease (treatment arm 1 only).

        Other eligibility criteria apply.