BMS-986158 + Ruxolitinib/Fedratinib for Myelofibrosis

Not currently recruiting at 144 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment, BMS-986158 (a BET inhibitor from Bristol-Myers Squibb), both alone and in combination with other medicines (Ruxolitinib or Fedratinib), for individuals with certain blood cancers, such as myelofibrosis. Myelofibrosis causes scar tissue to build up in the bone marrow, affecting blood cell production. Individuals with intermediate or high-risk blood cancer who have experienced side effects from previous treatments may be suitable candidates for this study. As a Phase 1/Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the drug BMS-986158, when combined with either Ruxolitinib or Fedratinib, is generally safe for people with myelofibrosis, a type of blood cancer. Most patients tolerate these drug combinations well and do not experience serious side effects. Common mild side effects include fatigue and nausea. These results suggest that the treatment is safe enough for further testing in clinical trials. However, individual experiences may vary. Prospective participants should discuss these findings with their doctor to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for myelofibrosis, which typically involve JAK inhibitors like ruxolitinib or fedratinib, the investigational drug BMS-986158 introduces a new mechanism of action by targeting bromodomain and extra-terminal (BET) proteins. This approach aims to modulate gene expression, potentially reducing disease symptoms and improving patient outcomes. Researchers are excited because this unique action could offer benefits beyond what current therapies provide, possibly addressing unmet needs in patients who do not respond adequately to existing treatments.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

Previous studies showed that BMS-986158, a drug that blocks proteins involved in cancer growth, holds promise when combined with either Ruxolitinib or Fedratinib for treating myelofibrosis. This trial will further explore these combinations. Participants may receive BMS-986158 with Ruxolitinib or BMS-986158 with Fedratinib. Research indicates these combinations can reduce disease signs and help manage symptoms in patients with intermediate or high-risk myelofibrosis. Early animal studies also demonstrated that these drugs could lower disease burden and inflammation. These findings suggest that combining BMS-986158 with Ruxolitinib or Fedratinib could be an effective treatment option. ^{1 2 3 5 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/623/502736/BMS-986158-a-Potent-BET-Inhibitor-in-Combination

BMS-986158, a Potent BET Inhibitor, in Combination with ... A potent BET inhibitor, in combination with Ruxolitinib or Fedratinib in patients (pts) with intermediate- or high-risk myelofibrosis (MF): updated results ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC10428227

S213: BMS-986158, A POTENT BET INHIBITOR, AS ... BMS-986158 is being evaluated in pts with MF, alone and in combination with JAKi ruxolitinib (RUX) or fedratinib (FED), in the CA011-023 study (NCT04817007).

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123052278

BMS-986158, a Potent BET Inhibitor, in Combination with ... These updated analyses of study CA011-023 show that BMS-986158+RUX in 1L MF and BMS-986158+FED in 2L MF continue to be well tolerated, with most patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04817007

NCT04817007 | A Study to Assess the Safety and ... The purpose of this study is to assess the safety, tolerability, and efficacy of BMS-986158 alone and in combination with either Ruxolitinib or Fedratinib ...

5. journals.lww.com journals.lww.com/hemasphere/fulltext/2023/08003/s213__bms_986158,_a_potent_bet_inhibitor,_as.115.aspx

s213: bms-986158, a potent bet inhibitor, as monotherapy ... BET inhibitors (BETi) alone and combined with JAKi demonstrate reduction in inflammatory signalling and disease burden in mouse MF models, and inhibition of BET ...

6. bmsstudyconnect.com bmsstudyconnect.com/no/en/clinical-trials/NCT04817007.html

A Study to Assess the Safety and Tolerability of BMS-986158 ... The purpose of this study is to assess the safety, tolerability, and efficacy of BMS-986158 alone and in combination with either Ruxolitinib ...