Masitinib for Systemic Mastocytosis

Not currently recruiting at 22 trial locations

Overseen By Daniele Roosalem

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AB Science

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Cutaneous mastocytosis, SM-AHNMD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the oral drug masitinib is safe and effective for individuals with smouldering or indolent systemic mastocytosis who experience severe symptoms like itching, flushing, or depression, despite other treatments. Participants will receive either masitinib or a placebo, alongside their current symptom-relief treatments. Eligible individuals have systemic mastocytosis with abnormal mast cells in at least two organs and have found existing treatments ineffective. Those experiencing severe symptoms that impact daily life might find this trial suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, it mentions that you must have had treatment failure with certain medications, so you might need to continue those treatments.

Is there any evidence suggesting that masitinib is likely to be safe for humans?

Research has shown that masitinib was tested for safety in earlier studies. This medicine inhibits certain proteins that promote cancer cell growth. In studies with dogs that had mast cell tumors, masitinib proved safe and helped slow tumor growth. Although these results come from animal studies, they provide some insight into the drug's safety.

For humans, masitinib has been tested on individuals with various types of mastocytosis, a condition characterized by an excess of mast cells in the body. Past patients generally tolerated the treatment well. Common side effects included nausea and tiredness, but most people managed these.

Safety information from its use in other conditions also supports its general safety. Since this trial is in a later phase, earlier studies have shown the treatment to be relatively safe for humans. However, any treatment can have side effects, so discussing these with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for systemic mastocytosis, which often focus on symptom management and include medications like antihistamines and corticosteroids, masitinib offers a novel approach by targeting the underlying issue. Masitinib is a tyrosine kinase inhibitor, which means it works by blocking specific enzymes (kinases) that are involved in the overproduction and activity of mast cells, a key problem in systemic mastocytosis. This targeted action has the potential not only to relieve symptoms but also to address the disease's root cause, making researchers hopeful for more comprehensive and effective management of this condition.

What evidence suggests that masitinib might be an effective treatment for systemic mastocytosis?

Studies have shown that masitinib is a promising treatment for slow-growing forms of systemic mastocytosis. It targets a specific part of the cells involved in the condition. In this trial, participants will receive either masitinib or a placebo, both as an add-on to best supportive care. Research indicates that masitinib is effective and safe for long-term use in similar conditions. It helps manage severe symptoms, especially when other treatments have failed. The drug is well-tolerated, allowing patients to take it long-term with minimal side effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Cristina Bulai Livideanu, MD, MSc

Principal Investigator

Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France

Are You a Good Fit for This Trial?

This trial is for patients with severe symptoms of systemic mastocytosis, specifically the smoldering or indolent types, who haven't responded to treatments like antihistamines or antidepressants. They must have a certain level of itching, flushing, or depression and evidence of abnormal mast cells in at least two organs.

Inclusion Criteria

I have been diagnosed with systemic mastocytosis based on tissue analysis.

I have too many or abnormal mast cells in at least two organs.

I have severe itching, flushing, or depression due to mastocytosis.

Exclusion Criteria

Treatment with any investigational agent within 8 weeks prior to screening

I have a type of mastocytosis (skin, systemic with another blood disease, mast cell leukemia, or aggressive).

I have been treated with a Tyrosine Kinase Inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral masitinib or placebo for 24 weeks with dose escalation every 4 weeks

24 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Masitinib

Trial Overview The study compares masitinib—a drug that targets specific enzymes—to a placebo in treating systemic mastocytosis when usual symptom relief doesn't work. Participants will receive either masitinib or a placebo alongside their supportive care regimen.

How Is the Trial Designed?

Group I: Masitinib & BSC Experimental Treatment 2 Interventions

Experimental Arm: Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Group II: Placebo & BSC Placebo Group 2 Interventions

Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Masitinib is already approved in European Union, United States for the following indications:

Approved in European Union as Masivet for:

• Mast cell tumors in dogs

Approved in United States as Kinavet for:

• Mast cell tumors in dogs

Who Is Running the Clinical Trial?

AB Science

Lead Sponsor

Trials

39

Recruited

15,700+

Published Research Related to This Trial

Masitinib, a new potential treatment for systemic mastocytosis (SM), is more selective for c-kit receptors compared to other tyrosine kinase inhibitors, which may enhance its effectiveness in targeting the disease.

The drug shows promise in inhibiting mast cell degranulation, cytokine production, and migration, suggesting it could be a significant therapeutic option for certain patients with SM, although further research is needed to establish response measurement methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of masitinib for treating systemic mastocytosis. Laforgia, M., Marech, I., Nardulli, P., et al.[2021]

Avapritinib, a selective oral inhibitor targeting the mutated tyrosine kinase in systemic mastocytosis, has shown promising safety and efficacy in early Phase I and II trials, even for patients who did not respond to previous therapies.

Current studies are primarily focused on patients with aggressive forms of systemic mastocytosis, with new trials beginning for those with indolent forms, indicating a potential expansion of treatment options in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avapritinib in the Treatment of Systemic Mastocytosis: an Update. Below, S., Michaelis, LC.[2021]

In a phase 3 study involving 135 patients with indolent or smouldering systemic mastocytosis, masitinib demonstrated a significant cumulative response of 18.7% compared to 7.4% for placebo, indicating its efficacy in improving severe symptoms.

Masitinib was generally well tolerated, with common side effects including diarrhea and rash, but no life-threatening toxicities were reported, suggesting a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lortholary, O., Chandesris, MO., Bulai Livideanu, C., et al.[2021]

Avapritinib is a highly selective inhibitor of the KIT D816V mutation and has been approved for treating advanced systemic mastocytosis (AdvSM), showing the ability to achieve complete and durable clinical responses in patients.

The phase 1 EXPLORER and phase 2 PATHFINDER trials confirmed that avapritinib can lead to molecular remission of the KIT D816V mutation, although managing AdvSM can be complicated due to its diverse mutational landscape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avapritinib for advanced systemic mastocytosis. Gotlib, J., Reiter, A., DeAngelo, DJ.[2023]

Avapritinib is an effective treatment for advanced systemic mastocytosis (AdvSM), showing significant activity even after multiple prior treatments, and can lead to rapid and profound responses in patients.

The use of avapritinib as a bridging strategy to allogeneic transplant is promising, but careful monitoring for side effects is essential, particularly in patients who have undergone extensive previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical experience of compassionate use program for avapritinib: implications for drug positioning in the therapeutic scenario of systemic mastocytosis. Mannelli, F., Crupi, F., Zanotti, R., et al.[2023]

Masitinib mesylate effectively inhibits the proliferation of canine mammary tumor (CMT) cells in a concentration-dependent manner, demonstrating its potential as a treatment for this type of cancer in dogs.

The mechanism of action involves inducing apoptosis and cell cycle arrest, as well as reducing levels of vascular endothelial growth factor (VEGF) and the Ki-67 proliferation index, indicating that masitinib could be a promising therapeutic option for canine mammary cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Tyrosine Kinase Inhibitor-masitinib Mesylate on Canine Mammary Tumour Cell Lines. Ustun-Alkan, F., Bakırel, T., Üstüner, O., et al.[2022]

In a study of 39 dogs with macroscopic mast cell tumors treated with masitinib, 82.1% showed a clinical response, with 38.5% achieving complete remission and 43.6% showing partial response, indicating its efficacy.

Masitinib was generally well-tolerated, with a median survival time of 159 days, although 64.1% of dogs experienced adverse effects, the most common being elevated liver enzymes and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response of masitinib mesylate in the treatment of canine macroscopic mast cell tumours. Grant, J., North, S., Lanore, D.[2021]

Masitinib is a highly selective tyrosine kinase inhibitor that shows greater activity against the KIT receptor compared to imatinib, with a half inhibitory concentration (IC(50)) of 200 nM, indicating its potential effectiveness in treating conditions like cancer and mastocytosis.

In animal studies, masitinib demonstrated a favorable safety profile, showing no signs of cardiotoxicity or genotoxicity, and effectively inhibited tumor growth in mice with KIT mutations, suggesting it could be a safer alternative to other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. Dubreuil, P., Letard, S., Ciufolini, M., et al.[2022]

Masitinib, a selective oral tyrosine kinase inhibitor, showed significant efficacy in reducing symptoms associated with indolent mastocytosis in a study of 25 patients over 12 weeks, with improvements in flushes, depression, and pruritus by 64%, 43%, and 36% respectively.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, although one patient experienced a serious but reversible side effect (agranulocytosis), indicating that masitinib could be a viable long-term treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Paul, C., Sans, B., Suarez, F., et al.[2021]

Masitinib mesylate is a selective tyrosine kinase inhibitor approved for treating unresectable canine mast cell tumors, showing efficacy by targeting c-Kit receptor mutations that drive cancer progression.

Currently under investigation for various human cancers, masitinib's anti-proliferative effects and safety profile suggest it could be a significant advancement in translational oncology, bridging veterinary and human cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Masitinib (AB1010), from canine tumor model to human clinical development: where we are? Marech, I., Patruno, R., Zizzo, N., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21108325/

Masitinib for the treatment of systemic and cutaneous ... Masitinib is a promising treatment for indolent forms of mastocytosis with handicap and indicates acceptable tolerability for long-term treatment regimens.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842813002667

Masitinib (AB1010), from canine tumor model to human ... Masitinib mesylate (AB1010) is a novel potent and selective tyrosine kinase inhibitor, targeting mainly wild-type and mutated c-Kit receptor (c-KitR).

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.0190.x

Masitinib is Safe and Effective for the Treatment of Canine ... Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.

4. researchgate.net researchgate.net/publication/248704423_Masitinib_mesylate_for_metastatic_and_non-resectable_canine_cutaneous_mast_cell_tumours

Masitinib mesylate for metastatic and non-resectable ... A single phase I trial of this drug combination has shown promise in its efficacy and safety for treating mast cell tumours (Robat et al. 2012).

5. ema.europa.eu ema.europa.eu/en/documents/assessment-report/masipro-epar-refusal-public-assessment-report_en.pdf

Masipro, INN - masitinib - European Medicines Agency The proposed mode of action of Masitinib mesylate in the pathology of indulgent systemic mastocytosis is shown in the figure below: Page 18 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23845124/

Masitinib mesylate for metastatic and non-resectable ... Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non-metastatic grade II and III canine mast cell tumours (MCTs).

7. ovid.com ovid.com/journals/jovim/fulltext/10.1111/j.1939-1676.2008.0190.x~masitinib-is-safe-and-effective-for-the-treatment-of-canine

Masitinib is Safe and Effective for the Treatment of Canine ... Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT. Mast cell ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.21894

Masitinib for the treatment of systemic and cutaneous ... Eligible patients were aged >18 years, had previously documented indolent systemic, smouldering systemic or cutaneous mastocytosis as per the ...