INCB57643 + Ruxolitinib for Myelofibrosis

Overseen By Mahesh Swaminathan, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: BET inhibitors, JAK inhibitors

Disqualifiers: Splenectomy, Active infections, Liver cirrhosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination, INCB57643 (an experimental treatment) and ruxolitinib, for treating myelofibrosis, a condition where scar tissue builds up in the bone marrow, affecting blood cell production. Researchers aim to determine the effectiveness of these drugs in patients who haven't used similar treatments before. Ideal candidates for this trial include those diagnosed with myelofibrosis, who have not tried JAK inhibitors (drugs that block signals promoting inflammation) or BET inhibitors, and who experience noticeable symptoms like an enlarged spleen or fatigue. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, systemic anticancer treatments other than hydroxyurea and anagrelide must be stopped at least 2 weeks before starting the study drugs. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that INCB57643 + Ruxolitinib is likely to be safe for humans?

Research has shown that the combination of INCB57643 and ruxolitinib is promising in terms of safety and tolerability. In earlier studies, patients with myelofibrosis tolerated this combination well. Some patients experienced improvements in symptoms such as anemia and reduced spleen size.

Ruxolitinib, a key component of this treatment, has been used for over ten years to treat myelofibrosis and is generally considered safe. However, side effects like low blood cell counts or infections can occur. Although INCB57643 is newer, early findings suggest it can be safely combined with ruxolitinib.

This trial is in Phase 2, indicating that the treatment has passed initial safety tests. Ongoing studies remain essential to confirm its safety and effectiveness for a broader population. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about INCB57643 combined with Ruxolitinib for treating myelofibrosis because this combination targets the condition in a novel way. Unlike existing treatments that primarily focus on reducing symptoms by inhibiting the JAK pathway, this duo introduces INCB57643, a BET inhibitor, which may interfere with the disease's progression by targeting gene expression. This unique mechanism could potentially offer better disease control and improve quality of life for patients with myelofibrosis, making it a promising advancement over current standard of care options.

What evidence suggests that INCB57643 + ruxolitinib could be an effective treatment for myelofibrosis?

Research shows that using INCB57643 with ruxolitinib, the combination studied in this trial, may help treat myelofibrosis. Studies have found that this combination can reduce symptoms such as enlarged spleen and anemia. Patients taking these drugs together have reported good tolerance and positive effects. Real-world evidence supports ruxolitinib's ability to improve myelofibrosis symptoms and extend patient survival. Early results suggest that adding INCB57643 might further enhance these benefits. ^{2 3 4 6 7}

Who Is on the Research Team?

Mahesh Swaminathan, MBBS

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients who have primary myelofibrosis or myelofibrosis and haven't been treated with JAK inhibitors before. Specific inclusion and exclusion criteria details are not provided, but typically these would outline the health status required to participate.

Inclusion Criteria

Agree to use highly effective contraceptive methods

Written informed consent required

Life expectancy of more than 24 weeks

Exclusion Criteria

I have had my spleen removed.

I have been treated with a JAK inhibitor like ruxolitinib.

I do not have an active or chronic infection with TB, HIV, Hepatitis B, or Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCB57643 in combination with Ruxolitinib for 24 weeks to evaluate splenic response rate

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for adverse events and overall response rate through study completion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• INCB57643
• Ruxolitinib

Trial Overview The study is testing a combination of two drugs: INCB57643, which is a BET inhibitor, and Ruxolitinib. The goal is to see how effective this combo is for patients who have never taken JAK inhibitors.

How Is the Trial Designed?

Group I: INCB+ R Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Ruxolitinib is an effective oral treatment for intermediate- or high-risk myelofibrosis, targeting JAK1 and JAK2 to reduce spleen size and improve symptoms, as demonstrated in Phase III trials with significant improvements in quality of life and overall survival.

The treatment has a manageable safety profile, with common side effects including anemia and thrombocytopenia, and requires dosage adjustments based on platelet counts, allowing for personalized patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. Swaim, SJ.[2021]

Ruxolitinib, the first approved treatment for myelofibrosis (MF), has shown significant improvements in spleen size and related symptoms in patients, based on results from Phase I/II and Phase III clinical trials involving direct comparisons to placebo and best available therapy.

While ruxolitinib is effective, it can cause side effects like cytopenias, which can be managed with dose adjustments, and there have been rare cases of infections related to immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ruxolitinib for myelofibrosis. Santos, FP., Verstovsek, S.[2021]

In a study of 104 patients with intermediate- and high-risk myelofibrosis, ruxolitinib demonstrated significant efficacy, with over 62% of patients showing a reduction in spleen size after 24 weeks, and high survival rates at 48 weeks (91% progression-free survival).

While ruxolitinib was effective, it was associated with notable safety concerns, including a high incidence of adverse events (62.5% of patients experienced serious AEs) and a 19.2% occurrence of second malignancies, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. Tavares, R., Souza, CA., Paley, C., et al.[2021]

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

Ruxolitinib is an effective oral JAK1 and JAK2 inhibitor that has been shown to significantly reduce spleen size and improve symptoms in patients with myelofibrosis (MF), based on randomized phase III studies.

The treatment is generally well-tolerated, with manageable side effects like anemia and thrombocytopenia, leading to its approval by the FDA for intermediate or high-risk myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. Mascarenhas, J., Mughal, TI., Verstovsek, S.[2021]

Ruxolitinib, an oral JAK1 and JAK2 inhibitor, has transformed the treatment of myelofibrosis (MF) since its approval, demonstrating significant clinical benefits in patients as shown in the phase 3 COMFORT-I/II trials.

Over the past 10 years, extensive research on ruxolitinib has enhanced the understanding of MF and its management, paving the way for future combination therapies to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years after ruxolitinib approval for myelofibrosis: a review of clinical efficacy. Pemmaraju, N., Bose, P., Rampal, R., et al.[2023]

Ruxolitinib is an effective oral treatment for myelofibrosis, leading to significant reductions in spleen size and symptom burden for most patients, and may improve survival rates regardless of JAK2 V617F mutation status.

The main side effects of ruxolitinib include thrombocytopenia (low platelet count) and anemia, and its metabolism can be affected by other medications that inhibit the CYP3A4 enzyme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib. Becker, H., Engelhardt, M., von Bubnoff, N., et al.[2021]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a study of 219 patients with myelofibrosis, ruxolitinib demonstrated a significant efficacy advantage over the best available therapy, with 28% of patients achieving at least a 35% reduction in spleen volume at 48 weeks, compared to 0% in the control group.

Ruxolitinib not only reduced spleen size but also improved overall quality of life and disease symptoms, with manageable side effects, primarily hematologic issues like thrombocytopenia and anemia, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. Harrison, C., Kiladjian, JJ., Al-Ali, HK., et al.[2022]

In a phase 2 trial involving 51 patients with myelofibrosis who were intolerant to ruxolitinib, 43.2% of those treated with the novel JAK inhibitor jaktinib showed a significant reduction in spleen volume after 24 weeks.

Jaktinib also improved symptoms related to myelofibrosis, with 61.8% of patients experiencing a notable decrease in total symptom scores, although it was associated with some serious adverse events, including anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhou, H., Duan, M., et al.[2023]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been the standard treatment for intermediate or high-risk myelofibrosis (MF) since its FDA approval in 2011, demonstrating significant efficacy in improving patient outcomes based on data from the phase 3 COMFORT trials.

The review highlights the importance of dose optimization and management of common side effects, such as anemia and thrombocytopenia, to maximize the safety and clinical benefits of ruxolitinib, supported by findings from subsequent trials like JUMP, ROBUST, EXPAND, and REALISE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. Verstovsek, S., Mesa, RA., Livingston, RA., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06619522

A Phase 2 Study of INCB57643 (BET Inhibitor) in ... Primary Objective: To evaluate splenic response rate by imaging after 24 weeks of treatment. Secondary Objectives: To evaluate splenic response rate by ...

2. onclive.com onclive.com/view/incb057643-ruxolitinib-shows-early-tolerability-efficacy-in-advanced-myelofibrosis

INCB057643 ± Ruxolitinib Shows Early Tolerability ... INCB057643 has shown encouraging clinical activity and favorable tolerability as both a single agent and add-on to ruxolitinib (Jakafi) in patients with ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08192

INCB057643 (BET inhibitor) in Combination with ... This phase II trial tests how well INCB057643 in combination with ruxolitinib works in treating patients with myelofibrosis.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39837682/

A Review of Real-World Experience With Ruxolitinib for ... Real-world evidence supports the effectiveness of ruxolitinib in improving splenomegaly and MF symptoms while significantly increasing overall survival.

5. pharmacytimes.com pharmacytimes.com/view/incb057643-in-combination-with-ruxolitinib-improves-symptoms-in-patients-with-myelofibrosis

INCB057643 in Combination with Ruxolitinib Improves ... INCB057643 (Incyte Corp) as a monotherapy or in combination with ruxolitinib (Jakafi; Incyte Corp) yielded favorable improvements in anemia, spleen size, and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04279847

Study Details | NCT04279847 | Safety and Tolerability ... The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of INCB057643 as monotherapy or combination with ruxolitinib for ...

7. withpower.com withpower.com/trial/phase-2-primary-myelofibrosis-2-2025-952d1

INCB57643 + Ruxolitinib for Myelofibrosis Ruxolitinib, also known as Jakafi or Jakavi, has been used for over a decade to treat myelofibrosis and is generally considered safe, though it can cause side ...