Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a Phase III multi-center, randomized, two-arm parallel-group, double-blind,
placebo-controlled study of MBG453 or placebo added to azacitidine in adult subjects with
intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic
Myelomonocytic Leukemia-2 (CMML-2) who have an indication for treatment with azacitidine in
first-line setting and are not eligible for intensive chemotherapy or hematopoietic stem cell
transplantation (HSCT) according to medical judgment by the investigator.
The purpose of the current study is to assess clinical effects of MBG453 in combination with
azacitidine in adult subjects with IPSS-R intermediate, high, very high risk MDS and CMML-2.
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Leukemia/heme
Enrollment Eligibility
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study
- Age ≥ 18 years at the date of signing the informed consent form
- Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO
2016 classification (Arber et al 2016) by local investigator assessment with one of
the following Prognostic Risk Categories, based on the revised International
Prognostic Scoring System (IPSS-R):
- Very high (> 6 points)
- High (> 4.5 - ≤ 6 points)
- Intermediate (> 3 - ≤ 4.5 points) Or Morphologically confirmed diagnosis of
Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al
2016, including persistent monocytosis) by local investigator assessment with WBC
< 13 x 109/L at time of initial diagnosis
- Indication for azacitidine treatment according to the investigator, based on local
standard medical practice and institutional guidelines for treatment decisions
- Not eligible at time of screening for intensive chemotherapy according to the
investigator, based on local standard medical practice and institutional guidelines
for treatment decisions, including assessment of individual clinical factors such as
age, comorbidities and performance status
- Not eligible at time of screening for hematopoietic stem cell transplantation (HSCT)
according to the investigator, based on local standard medical practice and
institutional guidelines for treatment decisions, including assessment of individual
clinical factors such as age, comorbidities, performance status, and donor
availability
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
- Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune
checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer
vaccines is allowed except if the drug was administered within 4 months prior to
randomization
- Previous first-line treatment for intermediate, high, very high risk myelodysplastic
syndromes (based on IPSS-R) or CMML with any antineoplastic agents including for
example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as
decitibine and azacitidine. However, previous treatment with hydroxyurea or
leukopheresis to reduce WBC count is allowed prior to randomization.
- Investigational treatment received within 4 weeks or 5 half-lives of this
investigational treatment, whatever is longer, prior to randomization. In case of a
checkpoint inhibitor: a minimal interval of 4 months prior to randomization is
necessary to allow randomization.
- Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber
et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3
- Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and
extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on
WHO 2016 classification (Arber et al 2016)
- Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber
et al 2016)
- History of organ or allogeneic hematopoietic stem cell transplant
Other protocol-defined Inclusion/Exclusion Criteria may apply.