BMS-986158 + Ruxolitinib/Fedratinib for Myelofibrosis

Recruiting at 132 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Disqualifiers: Pregnancy, Breastfeeding, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

216 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BMS-986158 for patients with high-risk blood cancer. It aims to see if the drug works better alone or when combined with existing treatments, Ruxolitinib and Fedratinib. Ruxolitinib is the first FDA-approved JAK inhibitor for myeloproliferative neoplasms, effective in controlling symptoms and improving splenomegaly, but many patients develop disease progression with long-term use.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination BMS-986158 and Ruxolitinib/Fedratinib for treating myelofibrosis?

Research shows that combining a BET inhibitor like Pelabresib with Ruxolitinib improved spleen size and symptoms in myelofibrosis patients more than using Ruxolitinib alone. This suggests that a similar combination with BMS-986158, another BET inhibitor, might also be effective. ^{1 2 3 4 5}

What safety information is available for the combination of BMS-986158 and Ruxolitinib/Fedratinib in treating myelofibrosis?

Fedratinib, a JAK2 inhibitor, has been associated with common side effects like diarrhea, nausea, anemia (low red blood cell count), and vomiting. It also carries a warning for the risk of serious brain conditions, such as Wernicke encephalopathy, especially in patients with poor nutrition or gastrointestinal issues. Pelabresib, a BET inhibitor, is being studied in combination with ruxolitinib, but specific safety data for this combination is not detailed in the available research. ^{1 3 6 7 8}

How is the drug BMS-986158 combined with Ruxolitinib/Fedratinib unique for treating myelofibrosis?

The combination of BMS-986158, a BET inhibitor, with Ruxolitinib or Fedratinib, which are JAK inhibitors, is unique because it targets both the BET and JAK pathways, potentially offering enhanced efficacy in reducing symptoms and spleen size in myelofibrosis compared to JAK inhibitor monotherapy. ^{1 2 6 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with a type of blood cancer called myelofibrosis, who are at intermediate or high risk. They must not have unresolved serious side effects from previous treatments and agree to use contraception if needed. Pregnant or breastfeeding women, those with acute illnesses or uncontrolled chronic conditions are excluded.

Inclusion Criteria

Must agree to follow specific methods of contraception, if applicable

My side effects from previous treatments have mostly gone away or are stable.

I have been diagnosed with a type of myelofibrosis.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have any severe or unmanaged chronic illnesses.

There are other criteria set by the study that determine if you can participate or not.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive BMS-986158 in combination with either Ruxolitinib or Fedratinib

8-12 weeks

Treatment Part 2

Participants receive BMS-986158 in combination with either Ruxolitinib or Fedratinib and BMS-986158 alone

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BMS-986158
• Fedratinib
• Ruxolitinib

Trial Overview The study tests the safety and effectiveness of BMS-986158 alone, and in combination with Ruxolitinib or Fedratinib. Participants will be divided into two parts: one part receiving combinations and the other receiving BMS-986158 alone to compare outcomes.

Participant Groups

Group I: Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicable Experimental Treatment 2 Interventions

Group II: Part 2B1: BMS-986158 + Fedratinib Experimental Treatment 2 Interventions

Group III: Part 2A3: BMS-986158 + Ruxolitinib Experimental Treatment 2 Interventions

Group IV: Part 2A2 Add-On: BMS-986158 + Ruxolitinib Experimental Treatment 2 Interventions

Group V: Part 2A1: BMS-986158 + Ruxolitinib Experimental Treatment 2 Interventions

Group VI: Part 1B: BMS-986158 + Fedratinib Experimental Treatment 2 Interventions

Group VII: Part 1A: BMS-986158 + Ruxolitinib Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a phase I/II study involving 27 patients with relapsed or refractory acute leukemias, ruxolitinib was found to be reasonably well tolerated, with the most common severe side effect being infections, particularly pneumonia.

One patient achieved a complete response with incomplete recovery of peripheral blood (CRp) at the highest dose of 200 mg b.i.d., indicating potential efficacy in this heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. Pemmaraju, N., Kantarjian, H., Kadia, T., et al.[2021]

Fedratinib has been approved by the FDA as a treatment for myelofibrosis, marking it as the second drug and second JAK inhibitor approved for this condition.

In the phase III JAKARTA trial, fedratinib significantly reduced symptoms of myelofibrosis compared to a placebo, but it carries a Boxed Warning for the risk of encephalopathy, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fedratinib Becomes New Option in Myelofibrosis. [2020]

In a pivotal phase III trial, fedratinib, an oral JAK2 inhibitor, demonstrated significant efficacy in treating myelofibrosis, with a 47% spleen volume response rate and a 40% symptom response rate at 24 weeks, compared to only 1% and 9% for placebo.

Fedratinib was generally well-tolerated, with common side effects including diarrhea, nausea, anemia, and vomiting, but notably, there were no cases of Wernicke encephalopathy reported in patients taking the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. Pardanani, A., Tefferi, A., Masszi, T., et al.[2022]

Ruxolitinib has been a key treatment for myelofibrosis for over a decade, but the emergence of new JAK inhibitors like fedratinib and pacritinib necessitates a clear understanding of what constitutes 'failure' of ruxolitinib therapy.

A consensus among experts suggests that in cases of ruxolitinib failure, either continuing ruxolitinib with an additional agent or switching to a different JAK inhibitor may be beneficial, highlighting the need for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. Bose, P., Kuykendall, AT., Miller, C., et al.[2023]

References

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

Matching-adjusted indirect comparison of the pelabresib-ruxolitinib combination vs JAKi monotherapy in myelofibrosis. [2023]

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

A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. [2021]

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

Pelabresib (CPI-0610): An Exciting Novel Drug for the Treatment of Myelofibrosis. [2023]

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

Fedratinib Becomes New Option in Myelofibrosis. [2020]

5. Greece pubmed.ncbi.nlm.nih.gov

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Current and future role of fedratinib in the treatment of myelofibrosis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. [2022]

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

Fedratinib in myelofibrosis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Real-world outcomes with fedratinib therapy in patients who discontinued ruxolitinib for primary myelofibrosis. [2023]