Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.

A Phase Ib/II, Open Label Study of 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 Acute myeloid leukemia (AML)/secondary AML who were in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (Minimal residual disease (MRD)+ post- Allogeneic hematopoietic stem cell transplantation (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

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: Sabatolimab; Drug: Azacitidine

Detailed Description

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 at >= Day 60 after 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 initiating 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13273
    • Novartis Investigative Site
• Germany
  • Freiburg im Breisgau, Germany, 79106
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Münster, Germany, 48149
    • Novartis Investigative Site
• Italy
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00165
      • Novartis Investigative Site
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sabatolimab 400mg; Safety cohort 1: Participants in this arm will receive sabatolimab 400mg intravenously every 4 weeks.	Biological: Sabatolimab; Sabatolimab is a solution in vial for IV infusion; Other Names: MBG453
Experimental: Sabatolimab 800mg; Safety cohort 2: Participants in this arm will receive sabatolimab 800mg intravenously every 4 weeks.	Biological: Sabatolimab; Sabatolimab is a solution in vial for IV infusion; Other Names: MBG453
Experimental: Sabatolimab + Azacitidine; Expansion cohort 3: Participants in this arm will receive sabatolimab at the recommended dose for expansion in combination with azacitidine.	Biological: Sabatolimab; Sabatolimab is a solution in vial for IV infusion; Other Names: MBG453; Drug: Azacitidine; Azacitidine comes in Vial for IV infusion or subcutaneous administration
Experimental: Sabatolimab; Expansion cohort 4: Participants in this arm will receive sabatolimab at the recommended dose for expansion.	Biological: Sabatolimab; Sabatolimab is a solution in vial for IV infusion; Other Names: MBG453
Experimental: Sabatolimab (adolescent cohort); Adolescent safety cohort (cohort 5): ≥12 to < 18 year old adolescent participants in this arm will receive sabatolimab at the recommended dose for expansion.	Biological: Sabatolimab; Sabatolimab is a solution in vial for IV infusion; Other Names: MBG453

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only)	Assessment of tolerability of sabatolimab in adults and adolescents in the post allogenic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.	From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days
Percentage of Adult Subjects With Absence of Hematologic Relapse Per Investigator Assessment (Safety Run-in and Expansion)	The percentage of adult participants for whom no evidence of hematologic relapse (no evidence of bone marrow blasts ≥5%, no evidence of reappearance of blasts in the blood; no evidence of development of extramedullary disease) has been documented after 6 cycles of study treatment or earlier discontinuation at the recommended dose of sabatolimab 800 mg.	From Cycle 1 Day 1 to end of Cycle 6; Cycle = 28 Days
Rate of Dose Limiting Toxicities (Safety Confirmation in Adolescent Cohort Only)	Assessment of tolerability of sabatolimab in adolescent participants in the post allogeneic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.	From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD)	Assessment of the treatment emergent grade III or IV aGvHD. Acute GvHD: Grade IV acute GvHD, Stage ≥3 lower GI acute GvHD (consistent with Grade III acute GvHD) or Stage ≥3 liver acute GvHD (consistent with Grade III GvHD).	From start of treatment to up to 36 months from last patient first treatment.
Incidence of Moderate to Severe Chronic GVHD (cGvHD)	Assessment of the treatment emergent moderate or severe cGvHD. Chronic GvHD: Moderate chronic GvHD of the lungs, Severe chronic GvHD.	From start of treatment to up to 36 months from last patient first treatment.
Peak of Serum Concentration (Cmax) Sabatolimab	Cmax is the maximal serum concentration of sabatolimab.	Cycle 1 Day 5 (end of infusion) and Cycle 3 Day 1 or Day 5 (end of infusion) and Cycle 24 Day 1 (end of infusion); Cycle =28 Days
Trough Serum Concentration of (Cmin) Sabatolimab	Cmin is the concentration of sabatolimab prior to next dosing or after end of treatment.	Adult cohorts: Pre-dose on Day 1 (safety run-in) or Day 5 (expansion) of Cycle 1, 3, 6 and 24 (safety run-in only); Adolescent cohort: Pre-dose on Day 1 of Cycle 1, 2, 3 and 6; Cycle = 28 Days
Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS)	Time from start of treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD or moderate to severe cGvHD requiring initiation of systemic treatment, morphologic/hematologic relapse, or death due to any cause, whichever occurs first	From start of treatment to up to 36 months from last patient first treatment
Relapse-free Survival (RFS)	Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first.	From start of treatment to up to 36 months from last patient first treatment
Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative	Percentage of participants with centrally confirmed MRD+ status at baseline converting to MRD- within the first 6 cycles of study treatment.	From start of treatment until end of Cycle 6 (Cycle = 28 Days)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Actual): August 22, 2024
• Study Completion (Actual): August 22, 2024

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; TIM-3; Azacitidine; MBG453; Allogeneic Hematopoietic Stem Cell Transplantation; MRD; Phase Ib/II; Sabatolimab; aHSCT; Measurable Residual Disease; Acute myeloid leukemia Hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Neoplasm, Residual; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; sabatolimab
• Other Study ID Numbers: CMBG453F12201; 2020-000869-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No