Study Description
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.
Interventions
Azacitidine
Sabatolimab
Eligibility Criteria
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
Study Location
Novartis Investigative Site
Recruiting
Las Palmas de Gran Canaria,35010,Spain
Worldwide Contacts
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