Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Reason given: In December 2023, Novartis decided to terminate the sabatolimab clinical development program early after Phase II (MDS1) and Phase III (MDS2) studies failed to meet their primary objectives. The termination was not due to safety concerns.
Key facts
- Where
- Beijing, Changchun, Chengdu, Guangzhou, Hangzhou, Jinan, Shanghai, Shenzhen, Suzhou, Tianjin, and Wuhan, ChinaSee the 11 sites
- Phase
- Phase 3
Where in China
- BeijingBeijing, ChinaNo longer taking part
- ChangchunChangchun, ChinaNo longer taking part
- ChengduChengdu, ChinaNo longer taking part
- GuangzhouGuangzhou, ChinaNo longer taking part
- HangzhouHangzhou, ChinaNo longer taking part
- JinanJinan, ChinaNo longer taking part
- ShanghaiShanghai, ChinaNo longer taking part
- ShenzhenShenzhen, ChinaNo longer taking part
- SuzhouSuzhou, ChinaNo longer taking part
- TianjinTianjin, ChinaNo longer taking part
- WuhanWuhan, ChinaNo longer taking part
Trial details
- Who runs it
- Novartis Pharmaceuticals
- Trial code
- NCT04266301
- Record updated
- 13 January 2026
- Original description
This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator.Read full original descriptionShow less
A Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who 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 was to assess clinical effects of MBG453 in combination with azacytidine in adult participants with IPSS-R intermediate, high, very high risk MDS and CMML-2.
Inclusion: 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: 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; 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; Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016); Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3; History of organ or allogeneic hematopoietic stem cell transplant; 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; 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).