385 Participants Needed

KRT-232 for Myelofibrosis

(BOREAS Trial)

Recruiting at 185 trial locations
YK
JM
Overseen ByJohn Mei
Age: 18+
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: Kartos Therapeutics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

Will I have to stop taking my current medications?

The trial information does not specify if 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 KRT-232 for Myelofibrosis?

The research highlights the effectiveness of JAK inhibitors, which are drugs that help reduce spleen size and improve symptoms in myelofibrosis patients. Although KRT-232 is not specifically mentioned, similar drugs in this category have shown benefits in managing myelofibrosis symptoms.12345

What safety data exists for KRT-232 (Navtemadlin) in humans?

Navtemadlin, also known as KRT-232, has been studied for its safety in humans, particularly in the context of myelofibrosis and other conditions. While specific safety data for KRT-232 is not detailed in the provided research, it is mentioned alongside other novel therapies being developed for myelofibrosis, suggesting ongoing evaluation of its safety profile.16789

How is the drug KRT-232 (Navtemadlin) different from other treatments for myelofibrosis?

KRT-232 (Navtemadlin) is unique because it is being studied as a non-JAK inhibitor monotherapy for patients who are resistant to or ineligible for JAK inhibitors, offering a potential new option for those with unmet clinical needs in myelofibrosis treatment.16101112

Eligibility Criteria

This trial is for patients with myelofibrosis who haven't responded to JAK inhibitor treatment. They should have a performance status score of 2 or less, indicating they can perform daily activities with some effort. The trial excludes those with significant heart issues, recent major organ transplants, brain injuries or strokes within the past 6 months, prior splenectomy, and previous treatments targeting MDM2 or p53.

Inclusion Criteria

I have been diagnosed with a form of myelofibrosis.
My condition is classified as high, intermediate-2, or intermediate-1 risk.
I have been treated with a JAK inhibitor, but it did not work for me.
See 1 more

Exclusion Criteria

I have previously received MDM2 or p53-targeted therapy.
I have had or plan to have a stem cell transplant from a donor.
I have had my spleen removed.
See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Phase 2 will determine the KRT-232 recommended dose and dosing schedule

24 weeks
21-day or 28-day cycles

Phase 3 Treatment

Phase 3 will test KRT-232 vs Best Available Therapy (BAT) with an option to cross-over to KRT-232 after 6 months

24 weeks
28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Treatment Details

Interventions

  • Best Available Therapy (BAT)
  • KRT-232
Trial OverviewThe study tests KRT-232 against Best Available Therapy (BAT) in myelofibrosis patients unresponsive to JAK inhibitors. Phase 2 determines the optimal dose of KRT-232; Phase 3 compares its effectiveness to BAT chosen by physicians. Participants are randomly assigned in a 2:1 ratio favoring KRT-232 and may switch from BAT to KRT-232 if needed.
Participant Groups
6Treatment groups
Experimental Treatment
Active Control
Group I: Part B Arm 1 KRT-232Experimental Treatment1 Intervention
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Group II: Part A Cohort 4bExperimental Treatment1 Intervention
KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
Group III: Part A Cohort 3Experimental Treatment1 Intervention
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Group IV: Part A Cohort 2Experimental Treatment1 Intervention
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Group V: Part A Cohort 1Experimental Treatment1 Intervention
KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Group VI: Part B Arm 2 Best Available TherapyActive Control1 Intervention
Best available therapy at the discretion of the investigator, on a 28-day cycle.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Kartos Therapeutics, Inc.

Lead Sponsor

Trials
17
Recruited
2,100+

Findings from Research

The discovery of the JAK2 V617F mutation has led to the development of targeted therapies for myelofibrosis (MF), with ruxolitinib being the first approved drug that significantly improves symptoms, reduces spleen size, and enhances survival in patients.
Several new JAK2 inhibitors and other therapeutic agents are in advanced testing stages, aiming to provide additional benefits over ruxolitinib, particularly in managing anemia and other disease features, marking a significant evolution in MF treatment options.
The new landscape of therapy for myelofibrosis.Gowin, K., Emanuel, R., Geyer, H., et al.[2021]
Selective JAK2 inhibitors have shown significant efficacy in reducing symptoms and splenomegaly in myelofibrosis patients, providing benefits that previous treatments could not achieve, although they may cause anemia and gastrointestinal issues.
The development of enhanced prognostic models is improving the ability to assess individual patient outcomes in myelofibrosis, which is crucial for balancing the benefits of new therapies against the risks of more invasive treatments like stem cell transplantation.
Assessing new therapies and their overall impact in myelofibrosis.Mesa, RA.[2016]
JAK inhibitors have significantly improved treatment options for myelofibrosis (MF) by alleviating symptoms, reducing spleen size, and enhancing quality of life, although they may lead to worsening blood cell counts (cytopenias).
Despite their benefits, JAK inhibitors do not stop disease progression or prevent the transformation to leukemia, and their impact on overall survival remains uncertain.
JAK inhibitors in the treatment of myelofibrosis.Levavi, H., Hoffman, R., Marcellino, BK.[2022]

References

The new landscape of therapy for myelofibrosis. [2021]
Assessing new therapies and their overall impact in myelofibrosis. [2016]
JAK inhibitors in the treatment of myelofibrosis. [2022]
Emerging drugs for the treatment of Myelofibrosis. [2021]
JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis. [2022]
Novel therapeutics for myelofibrosis. [2023]
Novel treatments for myelofibrosis: beyond JAK inhibitors. [2022]
Beyond Ruxolitinib: Fedratinib and Other Emergent Treatment Options for Myelofibrosis. [2020]
New strategies in myelofibrosis: the evolving paradigm of disease pathogenesis, prognostication and treatment. [2017]
10.United Statespubmed.ncbi.nlm.nih.gov
Clinical and laboratory features of myelofibrosis and limitations of current therapies. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
SOHO State of the Art Updates and Next Questions: Novel Therapies in Development for Myelofibrosis. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Looking forward: novel therapeutic approaches in chronic and advanced phases of myelofibrosis. [2023]