BMS-986253 for Myelodysplastic Syndrome

Overseen By Christine T McGowan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: DNMTi

Must not be taking: ESAs, Lenalidomide, Luspatercept

Disqualifiers: Uncontrolled illness, Autoimmune, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 months

2 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BMS-986253 for adults with myelodysplastic syndromes (MDS), especially those who haven't responded to other treatments. The drug works by blocking a protein that helps cancer cells grow. Researchers hope this will slow down the disease and improve patients' immune responses.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents, you must stop them at least 28 days before starting the study treatment.

What data supports the effectiveness of the drug BMS-986253 for Myelodysplastic Syndrome?

The combination of decitabine and cedazuridine, part of the treatment, has been shown to be effective for myelodysplastic syndromes (MDS) with similar effectiveness to intravenous decitabine, achieving complete remission in some patients. This combination has been approved for MDS treatment in the USA and Canada, demonstrating its effectiveness in clinical trials. ^{1 2 3 4 5}

Is BMS-986253 (Anti-IL-8, Decitabine and Cedazuridine, ASTX727, Inaqovi) safe for humans?

The combination of decitabine and cedazuridine (Inqovi) has been studied for safety in treating myelodysplastic syndromes (MDS) and showed similar safety profiles to intravenous decitabine. Common serious side effects included low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and fever with low white blood cell counts (febrile neutropenia). ^{1 2 4 6 7}

What makes the drug BMS-986253 for Myelodysplastic Syndrome unique?

The drug BMS-986253, combined with Decitabine and Cedazuridine, is unique because it offers an oral treatment option for Myelodysplastic Syndrome, which traditionally required intravenous administration. Cedazuridine enhances the oral bioavailability of Decitabine, making it as effective as the intravenous form, providing convenience and potentially improving patient adherence. ^{1 2 4 5 6}

Research Team

Alain Mina, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults 18+ with Myelodysplastic Syndromes (MDS) who meet specific criteria, including having received certain prior treatments for MDS. They must have a life expectancy over 6 months and be able to perform daily activities with some degree of independence. Participants need proper liver and kidney function and cannot be pregnant or breastfeeding.

Inclusion Criteria

My liver and kidney functions meet the trial's requirements.

I can take care of myself but might not be able to do active work.

I have MDS with specific blood counts and have had certain treatments.

Exclusion Criteria

I do not have active or uncontrolled autoimmune diseases.

I do not have any unmanaged ongoing illnesses.

I have low platelet counts that don't respond to transfusions or dangerously low white blood cell counts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BMS-986253 as an infusion on days 1 and 15 of each 28-day cycle, with some receiving additional DNMTi on days 2-6

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up visit 30 days after treatment ends and subsequent follow-ups via phone every 3-6 months

1 year

1 visit (in-person), phone follow-ups every 3-6 months

Treatment Details

Interventions

• BMS-986253
• Decitabine and Cedazuridine

Trial Overview The trial is testing BMS-986253 alone or combined with decitabine and cedazuridine in treating MDS. It's given in cycles, with infusions on specific days, alongside oral medication for some participants. The goal is to see if this new drug combination is safe and effective against MDS.

Participant Groups

Group I: Phase II Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 4 Interventions

Phase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.

Group II: Phase II Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 6 Interventions

Phase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.

Group III: Phase I Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 4 Interventions

Escalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.

Group IV: Phase I Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 6 Interventions

Escalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.

The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

In a phase 1 study involving 44 patients with myelodysplastic syndromes or chronic myelomonocytic leukaemia, the combination of oral decitabine and the CDA inhibitor cedazuridine successfully increased the bioavailability of decitabine, achieving pharmacokinetics similar to intravenous administration without increasing toxicity.

The study demonstrated that oral decitabine combined with cedazuridine produced effective dose-dependent demethylation and clinical responses comparable to intravenous decitabine, suggesting it could be a viable alternative treatment for myeloid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Savona, MR., Odenike, O., Amrein, PC., et al.[2019]

Luspatercept has shown significant efficacy in treating low-risk myelodysplastic syndromes (MDS), with 63% of patients experiencing hematological improvement and 38% achieving transfusion independence in clinical trials.

Oral decitabine combined with oral cedazuridine has demonstrated pharmacological equivalence to intravenous decitabine, achieving overall response rates of 60% and 43% in phase 2 and 3 trials for high-risk MDS, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. Usuki, K.[2022]

The combination of oral cedazuridine and decitabine (C-DEC) has been shown to have a similar pharmacokinetic and pharmacodynamic profile to parenteral decitabine, making it a promising alternative for treating higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

Phase 2 and phase 3 clinical trials confirmed the bioequivalence of C-DEC to parenteral decitabine, leading to FDA approval for its use in intermediate/high-risk MDS and CMML, highlighting its efficacy and safety as an oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. Patel, AA., Cahill, K., Saygin, C., et al.[2023]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

In a study of 99 patients with myelodysplastic syndromes (MDS), decitabine administered at a higher dose of 20 mg/m² daily for 5 days every 4 weeks resulted in a 32% overall response rate, indicating significant efficacy in treating MDS.

The outpatient regimen of decitabine not only provided comparable efficacy to the FDA-approved inpatient schedule but also allowed for more than half of the patients to show clinical improvement, suggesting a safe and effective alternative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. Steensma, DP., Baer, MR., Slack, JL., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. [2023]

3. England pubmed.ncbi.nlm.nih.gov

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. [2023]