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 was to test the hypothesis that preemptive treatment with sabatolimab, alone or in combination with azacitidine, when administered to participants with AML/secondary AML who were in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (MRD+ post-aHSCT), could 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 had 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 had been tapered off.

The study was planned to enroll approximately 59 participants and be conducted in two parts:

Part 1 was 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) was safe when administered in the post-aHSCT setting. For each dose level, once the required number of evaluable participants had been confirmed, enrollment would be halted until participants had completed the dose limiting toxicities (DLT) observation period (≥ 8 weeks following the first dose). Following the observation period for DLTs, a Safety Review Meeting was to 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 consisted 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 was to be administered at the recommended dose for expansion determined in Part 1.

After enrolling 4 participants in Part 2, Novartis took the decision to put enrollment in permanent halt and terminate the sabatolimab program. This decision was not driven by any safety concerns.

Eligibility Criteria:
Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* 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.
* Participants in complete remission (\< 5% bone marrow blasts, absence of circulating blasts, and absence of extramedullary disease) with MRD positivity by local assessment or by central assessment where required (e.g., USA sites), any time at ≥ Day 60 after aHSCT
* Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML
* 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.
* 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.
* 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
* 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:

* Prior exposure to TIM-3 directed therapy at anytime.
* History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
* Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
* Active acute GvHD grade III-IV according to standard criteria (Harris 2016).
* Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active severe chronic GvHD according to NIH consensus criteria.
* History of another primary malignancy that is currently clinically significant or currently requires active intervention. Participants who are receiving adjuvant therapy, such as hormone therapy, are eligible
* Any concurrent severe and/or active uncontrolled infection requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia)
* 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
* Live vaccine administered within 30 days prior to the first day of study treatment (Cycle 1 Day 1)
* 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