BMS-986253 in Myelodysplastic Syndromes

Clinical response was assessed by the assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes and reported with 95% confidence interval. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%. And cellularity and morphology not relevant. Stable disease is failure to achieve at least PR, but no evidence of progression for \>8 weeks. Progression is less than 5% blasts: ≥50% increase in blasts to \>5% blasts; 5%-10% blasts: ≥50% increase to 10% blasts; transfusion dependence. Relapse after CR or PR is at least 1 of the following: return to pre-treatment bone marrow blast percentage or decrement of ≥50% from maximum remission/response levels in granulocytes or platelets.

Time frame: Study treatment until occurrence of disease progression, death, or unacceptable toxicity or until response assessment on Cycle 7 day 1 (C7D1), a maximum of 6 cycles

Population: This outcome measure was not done because the company closed the study prior to phase II.

Overall response rate (ORR= Complete Remission (CR) + Partial Remission (PR) + \[marrow CR + hematologic improvement (HI\]) of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) after 6 cycles of therapy was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%. And cellularity and morphology not relevant.

Time frame: 6 months

Population: This outcome measure was not done because the company closed the study prior to phase II.

Safety as measured by incidence of adverse events (AEs) and serious adverse events (SAEs), and AEs leading to discontinuation, death, and laboratory abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 if life-threatening. Grade 5 is death related to adverse event.

Time frame: First 28 days and follow up after the end of the treatment cycle; approximately 2 months.

Population: 1/2 participants were enrolled but not treated.

OBD of BMS-986253 with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi), as determined by dose limiting toxicity (DLT) occurring by cycle 1 day 28 (C1D28). DLT is defined as any of the following: any grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dose reduction or withdrawal. OBD is the lowest tolerated dose level showing optimal biological activity, defined as maximal suppression of serum free IL-8 levels. The goal is to achieve IL-8 levels below the lower limit of detection of the assay in real time by Ultrasensitive immunoassay based on Quanterix Simoa technology. The lower limit of quantification = 0.86 pg/mL by Myriad-Rules Based Medicine (RBM).

Time frame: First 28 days (C1D28) on up to 30 days.

Population: 1/2 participants were enrolled but not treated.

RP2D of BMS-986253 with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi), as determined by dose -limiting toxicity (DLT) occurring by cycle 1 day 28 (C1D28). RP2D is defined as the optimal biological dose expected to be safe and of potential efficacy. It serves as a starting point for further investigations in future phase 2 clinical trials. DLT is defined as any of the following: ang grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dose reduction or withdrawal.

Time frame: First 28 days (C1D28)

Population: 1/2 participants were enrolled but not treated.

AUC is a measure of the serum concentration of drug BMS-986253 over time. It is used to characterize drug absorption.

Time frame: Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.

Population: Samples were stored but data were not analyzed because the manufacturer responsible for analyzing the samples terminated the study. No future data analysis will be conducted for samples stored for this terminated study.

Concentration of BMS-986253 at steady state in plasma.

Time frame: Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.

Population: Samples were stored but data were not analyzed because the manufacturer responsible for analyzing the samples terminated the study. No future data analysis will be conducted for samples stored for this terminated study.

Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

Time frame: Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.

Population: Samples were stored but data were not analyzed because the manufacturer responsible for analyzing the samples terminated the study. No future data analysis will be conducted for samples stored for this terminated study.

Cytogenetic Response was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes. Cytogenetic complete response is disappearance of the chromosomal abnormality without appearance of new ones. Cytogenetic partial response is at least 50% reduction of the chromosomal abnormality.

Time frame: Study treatment until occurrence of disease progression, death, or unacceptable toxicity or until response assessment on Cycle 7 day 1 (C7D1), a maximum of 6 cycles

Population: This outcome measure was not done because the company closed the study prior to phase II.

DFS is defined as time to relapse for participants who achieve complete remission (CR) using the Kaplan-Meier method. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted.

Time frame: Until study closure

Population: This outcome measure was not done because the company closed the study prior to phase II.

LFS is defined as progression to acute myeloid leukemia (AML) or death from any cause using the Kaplan-Meier method. Progression was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes using the Kaplan-Meier method and is defined as less than 5% blasts: ≥50% increase in blasts to \>5% blasts; 5%-10% blasts: ≥50% increase to 10% blasts; 10%-20% blasts: ≥50% increase to \>20% blasts; 20%-30% blasts: ≥50% increase to \>30% blasts and any of the following: At least 50% decrement from maximum remission/response in granulocytes or platelets, reduction in Hgb by ≥2 g/dL, and transfusion dependence.

Time frame: Until study closure

Population: This outcome measure was not done because the company closed the study prior to phase II.

Safety as measured by incidence of adverse events (AEs) and serious adverse events (SAEs), and AEs leading to discontinuation, death, and laboratory abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 if life-threatening. Grade 5 is death related to adverse event.

Time frame: 1 year

Population: This outcome measure was not done because the company closed the study prior to phase II.

OS is defined as death from any cause using the Kaplan-Meier method.

Time frame: Until study closure

Population: This outcome measure was not done because the company closed the study prior to phase II.

PFS is defined as disease progression or death from Myelodysplastic Syndromes (MDS). Progression was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes using the Kaplan-Meier method and is defined as less than 5% blasts: ≥50% increase in blasts to \>5% blasts; 5%-10% blasts: ≥50% increase to 10% blasts; 10%-20% blasts: ≥50% increase to \>20% blasts; 20%-30% blasts: ≥50% increase to \>30% blasts and any of the following: At least 50% decrement from maximum remission/response in granulocytes or platelets, reduction in Hgb by ≥2 g/dL, and transfusion dependence.

Time frame: Until study closure

Population: This outcome measure was not done because the company closed the study prior to phase II.

Time to best response (Complete Remission (CR), Partial Remission (PR), marrow CR + HI, HI) using the Kaplan-Meier method. Response was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%. And cellularity and morphology not relevant. Hematologic improvement (HI) is defined as: Erythroid response - at least 2 consecutive hemoglobin (hgb) measurements \>1.5 g/dL for a period of minimum 8 weeks in an observation period of 16-24 weeks compared with the lowest mean of 2 hgb measurements within 16 weeks before treatment onset. Platelet response - absolute increase of 30x10\^9/L for participants starting with \>20x10\^9/L platelets.

Time frame: Time to best response

Population: This outcome measure was not done because the company closed the study prior to phase II.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame: From first study intervention, study day 1, through study day 100 after the end of the treatment cycle; approximately 7 months.

Population: 1/2 participants were enrolled but not treated.

DLT is defined as any of the following: ang grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dose reduction or withdrawal.

Time frame: First 28 days

Population: 1/2 participants were enrolled but not treated.