Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.
Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.
The primary purpose of this study is to test the hypothesis that preemptive treatment with
 sabatolimab, alone or in combination with azacitidine, when administered to participants with
 AML/secondary AML who are in complete remission with positive measurable residual disease
 post-allogeneic hematopoietic stem cell transplantation (MRD+ post-aHSCT), can enhance the
 graft versus leukemia (GvL) response and prevent or delay hematologic relapse without an
 unacceptable level of treatment-emergent toxicities, including clinically significant acute
 and/or chronic graft-versus-host disease (GvHD) and immune-related adverse events
This is a phase Ib/II, open label, multi-center study of sabatolimab as monotherapy and in
 combination with azacitidine, in participants with AML/secondary AML who have received one
 aHSCT and achieved complete remission but MRD+, by local assessment, anytime between day 100
 and day 365 post-aHSCT and at least 2 weeks after immunosuppressive medications have been
 tapered off.

 The study will enroll approximately 59 participants and will be conducted in two parts:

 Part 1 is a Safety Run-in of approximately 20 participants, to assess whether sabatolimab as
 monotherapy at the two tested dose levels (400 mg and 800 mg intravenously Q4W) is safe when
 administered in the post-aHSCT setting. For each dose level, once the required number of
 evaluable participants has been confirmed, enrollment will be halted until participants have
 completed the DLT observation period (≥ 8 weeks following the first dose). Following the
 observation period for DLTs, a Safety Review Meeting will be conducted after each dose level
 to assess safety and determine the recommended dose for expansion to proceed with enrollment
 of additional cohorts in Part 2 of the study.

 Part 2 consists of sabatolimab monotherapy expansion cohort of approximately 13 participants,
 sabatolimab in combination with azacitidine cohort of approximately 20 participants, and an
 adolescent cohort of approximately 6 participants (≥ 12 years but < 18 years of age) with
 sabatolimab as monotherapy. Sabatolimab will be administered at the recommended dose for
 expansion determined in Part 1.
Inclusion Criteria:

 1. Signed informed consent must be obtained prior to participation in the study.

 2. At the date of signing the informed consent form (ICF), eligible participants must be
 ≥ 18 years for the adult cohorts; and ≥ 12 years old but < 18 years old for the
 adolescent cohort (cohort 5), which will open after completion of Safety Run-in.

 3. Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML

 4. Participants in complete remission (< 5% bone marrow blasts, absence of circulating
 blasts, and absence of extramedullary disease) with measurable residual disease (MRD)
 positivity by local assessment, at any time between day 100 and day 365 after
 allogeneic stem cell transplantation.

 5. Ability to provide a fresh bone marrow aspirate sample collected within 28 days from
 enrollment/randomization, and immediately shipped to a Novartis designated central
 laboratory for MRD testing.

 6. Systemic GvHD (graft versus host disease) prophylaxis or treatment [immunosuppressive
 treatment (IST)] completely tapered for at least two weeks prior to study entry.
 Prednisone dose ≤ 5 mg/day or equivalent corticosteroid dose is allowed.

 7. Participants who are found with MRD positivity while still on or tapering systemic
 GvHD prophylaxis or treatment, MRD positivity must be re-confirmed at least 2 week
 after the last dose of IST

 8. For the adult cohorts, participants must have an Eastern Cooperative Oncology Group
 (ECOG) performance status of 0, 1 or 2.

 For the adolescent cohort, participants must have a Karnofsky (age ≥ 16 years) or Lansky
 (age < 16 years) performance status score ≥ 50%.

 Exclusion Criteria:

 1. Prior exposure to TIM-3 directed therapy at anytime.

 2. History of severe hypersensitivity reactions to any ingredient of study drug(s)
 (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients

 3. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is
 controlled under antiviral therapy should not be excluded.

 4. Active acute GvHD grade III-IV according to standard criteria (Harris 2016).

 5. Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active
 severe chronic GvHD according to NIH consensus criteria.

 6. History of another primary malignancy that is currently clinically significant or
 currently requires active intervention.

 7. Any concurrent severe and/or active uncontrolled infection requiring parenteral
 antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis,
 or septicemia)

 8. Active autoimmune disease requiring systemic therapy (e.g. corticosteroids). Topical,
 inhaled, nasal and ophthalmic steroids are not prohibited. Replacement corticosteroids
 therapy is allowed and not considered a form of systemic treatment

 9. Live vaccine administered within 30 days prior to the first day of study treatment
 (Cycle 1 Day 1)

 10. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled
 diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease
 including dyspnoea at rest from any cause) or history of serious organ dysfunction or
 disease involving the heart, kidney, or liver

 Other protocol defined inclusion/exclusion criteria may apply