A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).

CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100\*109/L AND Neutrophils ≥ 1.0\*109/L AND Peripheral blasts 0%. Modified response criteria According to International Working Group (IWG) and as per World Health Organization (WHO) criteria for Myelodysplastic syndromes (MDS) as per investigator assessment.

Time frame: average of 7 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population) Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

PFS is defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment.

Time frame: approx. 32 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Duration of complete response is the time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized. Analysis was done on participants who experienced a complete remission.

EFS is defined as the time from randomization to lack of reaching complete response (CR) within the first 6 months, relapse from CR or death due to any cause, whichever occurs first. CR and relapse from CR were defined according to International Working Group (IWG) for Myelodysplastic Syndromes (MDS) as per Investigator assessment. For participants not reaching CR within the first 6 months, an EFS event at day 1 was considered.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent to treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Number of participants with at least one sample meeting the criteria at baseline. Anti-drug Antibody (ADA) prevalence equals ADA-positive at baseline.

Time frame: at baseline

Population: The immunogenicity prevalence set included all participants in the full analysis set with a determinant baseline IG sample.

Anti-drug Antibody (ADA) positive participants on-treatment was calculated as the number of participants with at least 1 on-treatment ADA-positive sample divided by the number of participants with a determinant baseline IG sample and at least one determinant post-baseline IG sample.

Time frame: approx. 48 months

Population: Included all participants in the immunogenicity prevalence set with a determinant baseline IG sample and at least one determinant post-baseline IG sample.

LFS is defined as the time from randomization to ≥ 20% blasts in bone marrow/peripheral blood (per World Health Organization (WHO) 2016 classification) or diagnosis of extramedullary acute leukemia or death due to any cause.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent to treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Time from randomization to death due to any cause

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent to treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Improvement in RBC/platelets transfusion independence. RBC/platelets transfusion independence rate is defined as the percentage of participants having received no RBC/platelets transfusions during at least 8 consecutive weeks after randomization.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized subjects were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

The total duration of all transfusion independence periods is the sum of each period of the transfusion independence. Platelets transfusions independence period is defined as the period for which participants having received no platelets transfusions during at least 8 consecutive weeks after randomization.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized. Analysis done only on participants with at least one period of platelets transfusion independence post-baseline.

PFS isdefined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause. This is an update of the Primary Outcome Measure PFS with data collected after assessment of the primary results.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

The total duration of all transfusion independence periods is the sum of each period of the transfusion independence. RBC transfusions independence period is defined as the period for which participants having received no RBC transfusions during at least 8 consecutive weeks after randomization.

Time frame: approx. 48 months

Population: Full Analysis Set (FAS): All randomized subjects were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized. Analysis done only on participants with at least one period of RBC transfusion independence post-baseline.

Percentage of complete remission (CR)/marrow Complete Remission (mCR)/partial remission (PR) & Hematological improvement (HI) as per investigator assessment according to IWG-MDS. CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100\*109/L AND Neutrophils ≥ 1.0\*109/L AND Peripheral blasts 0%. mCR: where the Bone marrow ≤5% blasts and blast count decrease by ≥50% compared to baseline with or without improved blood counts or with or without transfusions. PR: All CR criteria except bone marrow: ≥50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow \>5%. HI: restoration or enhancement of the function of the body's blood cell-producing system that must last as least 8 weeks. HI definition is based on modified Hematological Improvement per IWG-MDS criteria in MDS & is the combination of Erythroid response (HI-E), Platelet response (HI-P) & Neutrophil response (HI-N).

Time frame: approx. 32 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Pharmacokinetics (PK) of MBG453 when given in combination with hypomethylating agents (HMA)

Time frame: 0hr pre-dose on Day 8 of each cycle until cycle 6 and on Day 8 of cycles 9, 12, 18 and 24, 2hr post-dose on Day 8 of C1 and C3, EOT (approx. 48 months) and up to 150 day of the safety follow up period; 1 cycle = 28 days

Population: Pharmacokinetic analysis set (PAS) included all participants in the Safety Set in the MBG453 arm only, who had at least one evaluable PK concentration.

Time from randomization to the first documented CR

Time frame: Average of 7 months

Population: Full Analysis Set (FAS): All randomized participants were included in the FAS (intent-to-treat population). Participant data in the FAS were analyzed according to the treatment and stratum they were assigned to when they were randomized.

Deaths were collected from randomization until end of trial, approx. 48 months.

Time frame: from randomization until end of trial, approx. 48 months

Population: Clinical database population: All randomized participants: participants who died before treatment, during treatment and post-treatment.