NCT04266301

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)

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)

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 530 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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). The primary objective of this study was to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS was the time from randomization until death due to any cause. Participants were randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W plus azacitidine, Placebo IV Q4W plus azacitidine. The randomization was stratified into 4 groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2. All participants who discontinued both study treatments were to have entered a long-term post-treatment follow-up including response and PRO assessments, and/or survival follow-up for up to 5 years after the last participant was randomized. Participants were receiving treatment until they experienced progression of disease (including transformation to acute leukemia per WHO 2016 classification), experienced unacceptable toxicity or discontinued the study treatment for other reasons. Continuation of study treatment beyond progression (excluding transformation to acute leukemia: continuation in this case was not possible) could have been possible in selected participants.

Conditions

• Myelodysplastic Syndromes
• Leukemia, Myelomonocytic, Chronic

Interventions

Type	Name	Description
DRUG	Sabatolimab	A dose of MBG453 800 mg was administered intravenously (IV) every 4 weeks (Q4W).
DRUG	Azacitidine	A dose of Azacitidine 75 mg/m2 was administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.
DRUG	Placebo	A dose of placebo 800 mg was administered intravenously every 4 weeks (Q4W).

Timeline

• Start date: 2020-06-08
• Primary completion: 2024-10-02
• Completion: 2024-10-02
• First posted: 2020-02-12
• Last updated: 2026-01-13
• Results posted: 2025-12-12

Locations

149 sites across 36 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, Oman, Portugal, Russia, Saudi Arabia, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study