Avapritinib for Systemic Mastocytosis

Recruiting at 48 trial locations

Overseen By Blueprint Medicines

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Blueprint Medicines Corporation

Must not be taking: Cytoreductive, Antibody, Interferon, others

Disqualifiers: Cutaneous mastocytosis, Aggressive SM, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: Unknown

251 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but it does require that you have not taken certain treatments like cytoreductive therapy or investigational agents for a specific period before starting the trial. If you are on corticosteroids, your dose must be stable for at least 14 days.

What data supports the effectiveness of the drug Avapritinib for treating systemic mastocytosis?

Research shows that Avapritinib is effective in treating advanced systemic mastocytosis, with studies reporting an overall response rate of 71-75% and significant reductions in disease markers. The drug was generally well tolerated, with most side effects being mild to moderate. ^{1 2 3 4 5}

How is the drug Avapritinib unique in treating systemic mastocytosis?

Avapritinib is unique because it is a highly selective inhibitor of the KIT D816V mutation, which is present in most patients with advanced systemic mastocytosis. It has shown high response rates and can lead to complete remission, making it a potent option for patients who have undergone previous treatments. ^{1 2 4 6 7}

What is the purpose of this trial?

This trial is testing a new medication called avapritinib combined with the best possible care for patients with a condition called indolent systemic mastocytosis (ISM). These patients have symptoms that are not well managed by their current treatments. Avapritinib works by blocking certain proteins that cause abnormal cell growth and activity, aiming to improve symptom control.

Eligibility Criteria

This trial is for patients with indolent systemic mastocytosis (ISM) who haven't found relief from their symptoms through standard care. They must have a specific symptom score, confirmed ISM by pathology review, and be able to perform daily activities with minimal assistance. People can't join if they've had certain treatments recently, other SM subtypes, prior avapritinib use, or specific heart rhythm issues.

Inclusion Criteria

My current treatment hasn't relieved my symptoms.

I am on a stable dose of corticosteroids, not exceeding 20 mg/d prednisone or its equivalent, for at least 14 days.

My systemic mastocytosis was confirmed by a specialized lab review.

Exclusion Criteria

I haven't had radiotherapy or PUVA therapy in the last 14 days.

I have never been treated with avapritinib.

I haven't had specific cancer treatments in the required time before the trial starts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1 Treatment

Participants receive avapritinib or placebo in continuous 28-day cycles to determine optimal dosing

6 months

Monthly visits (in-person)

Part 2 Treatment

Participants receive avapritinib or placebo in continuous 28-day cycles to assess efficacy and safety

6 months

Monthly visits (in-person)

Part 3 Treatment

All participants receive avapritinib in continuous 28-day cycles

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Avapritinib
• Placebo

Trial Overview The study tests Avapritinib's effectiveness and safety against a placebo in ISM patients whose symptoms persist despite best supportive care. It's randomized and double-blind: neither doctors nor participants know who gets the real drug or placebo until the study ends. Everyone eventually receives Avapritinib during part three of the trial.

Participant Groups

Group I: (Part 3) Avapritinib RP2D + BSC Experimental Treatment 1 Intervention

Avapritinib will be administered orally in continuous 28-day cycles

Group II: (Part 2) Avapritinib RP2D + BSC Experimental Treatment 1 Intervention

Avapritinib will be administered orally in continuous 28-day cycles

Group III: (Part 1) Avapritinib Dose 3 + BSC Experimental Treatment 1 Intervention

Avapritinib will be administered orally in continuous 28-day cycles

Group IV: (Part 1) Avapritinib Dose 2 + BSC Experimental Treatment 1 Intervention

Avapritinib will be administered orally in continuous 28-day cycles

Group V: (Part 1) Avapritinib Dose 1 + BSC Experimental Treatment 1 Intervention

Avapritinib will be administered orally in continuous 28-day cycles

Group VI: (Part 2) Placebo + BSC Placebo Group 1 Intervention

Placebo will be administered orally in continuous 28-day cycles

Group VII: (Part 1) Placebo + BSC Placebo Group 1 Intervention

Placebo will be administered orally in continuous 28-day cycles

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

Approved in United States as Ayvakit for:

• Unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations
• Advanced systemic mastocytosis
• Indolent systemic mastocytosis

Approved in European Union as Ayvakit for:

• Unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations
• Advanced systemic mastocytosis
• Indolent systemic mastocytosis

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials

31

Recruited

6,000+

Findings from Research

In a phase I trial of avapritinib for advanced systemic mastocytosis, 72% of patients showed a positive response, with 56% achieving complete or partial responses, indicating strong efficacy.

The treatment was well-tolerated, with no patients stopping due to adverse events, which were mostly mild to moderate, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. [2019]

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]

Avapritinib, a selective inhibitor for the KIT D816V mutation, showed a high overall response rate of 71% in patients with advanced systemic mastocytosis (AdvSM) who had previously received systemic therapy, with a median time to response of 2.3 months.

The treatment was generally well tolerated, with 94% of patients experiencing treatment-related adverse events, mostly mild (grade 1/2), and 81% remaining on treatment after 6 months, indicating its safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Reiter, A., Schwaab, J., DeAngelo, DJ., et al.[2022]

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]

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]

References

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

Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. [2019]

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

Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. [2022]

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

Avapritinib in the Treatment of Systemic Mastocytosis: an Update. [2021]

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

Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. [2022]

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

Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. [2022]

6. England 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. [2023]

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

Avapritinib for advanced systemic mastocytosis. [2023]