Avapritinib for Systemic Mastocytosis

No longer recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Blueprint Medicines Corporation

Must not be taking: Midostaurin, TKIs, Hydroxyurea, others

Disqualifiers: Eosinophilia, Primary malignancy, Seizure disorder, 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

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

Duration: 10 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called avapritinib to evaluate its effectiveness for people with advanced systemic mastocytosis, a condition where certain blood cells grow uncontrollably. The trial aims to assess the safety and effectiveness of the medication for aggressive forms of the condition, including mast cell leukemia. Individuals diagnosed with aggressive systemic mastocytosis and high levels of tryptase (a protein) in the blood might be suitable candidates for this study. Participants will take avapritinib in tablet form daily in 28-day cycles. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important medical advancements.

Do I need to stop my current medications to join the trial?

The trial requires that you stop certain medications before joining. Specifically, you must not have taken cytoreductive therapy or investigational agents within 14 to 28 days before the screening biopsy, depending on the medication.

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

Research has shown that avapritinib is generally safe for people with systemic mastocytosis. Studies have found that this treatment is well-tolerated and can improve symptoms and quality of life for those with indolent systemic mastocytosis, while maintaining a good safety record. Additionally, updates on avapritinib for advanced systemic mastocytosis emphasize its lasting and favorable safety over time. While side effects can occur, evidence suggests that avapritinib is safe for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic mastocytosis?

Avapritinib is unique because it specifically targets the KIT D816V mutation, which is a common driver in systemic mastocytosis. Unlike traditional treatments that may not directly target this mutation, Avapritinib offers a more precise approach, potentially leading to more effective management of the disease. Researchers are excited about Avapritinib because it represents a new class of treatment that could offer improved outcomes for patients by directly addressing the underlying genetic cause of the condition.

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

Research shows that avapritinib, which participants in this trial will receive, may help treat advanced systemic mastocytosis (AdvSM). Earlier studies found that patients experienced noticeable improvements in symptoms, including skin problems. After 144 weeks of treatment, many patients continued to feel better and reported an improved quality of life. Most patients tolerated the treatment well and remained on it for an extended period. These results suggest that avapritinib could be effective for people with advanced forms of this condition. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced systemic mastocytosis, including aggressive forms and mast cell leukemia. Participants must have a serum tryptase level of at least 20 ng/mL and an ECOG performance status of 0-3. They should not have had recent cytoreductive therapy or certain other treatments, nor should they have severe kidney issues, seizure disorders, brain cancer, low platelet counts, a history of intracranial bleeding, abnormal heart rhythm or liver enzymes due to causes other than mastocytosis.

Inclusion Criteria

I have been diagnosed with a severe form of mastocytosis confirmed by a specialized committee.

Your blood test must show a level of tryptase higher than 20 ng/mL.

I can care for myself but may not be able to do active work.

Exclusion Criteria

My kidney function is significantly reduced.

I haven't taken any cancer-reducing drugs or experimental treatments within the last 14 days, or specific drugs like cladribine or antibody therapies within the last 28 days.

I have high eosinophil levels and a positive FIP1L1-PDGFRA test, or no prior imatinib treatment failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avapritinib (BLU-285) as an immediate release tablet, orally, continuously, in 28-day cycles

10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Approximately 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Avapritinib

Trial Overview The PATHFINDER study is testing the effectiveness and safety of Avapritinib (BLU-285), which targets specific mutations in tyrosine kinase involved in systemic mastocytosis. It's an open-label Phase 2 trial where all participants receive the drug without being compared to another treatment or placebo.

How Is the Trial Designed?

Group I: Avapritinib Experimental Treatment 1 Intervention

Avapritinib will be administered as an immediate release tablet, orally, continuously, in 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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9647833/

Efficacy and safety of avapritinib in previously treated patients ... Treatment-related adverse events (TRAEs) were observed in 94% of patients, most commonly grade 1/2; 57% had TRAEs of at least grade 3; 81% remained on treatment ...

2. prnewswire.com prnewswire.com/news-releases/blueprint-medicines-announces-data-reinforcing-sustained-clinical-efficacy-and-well-tolerated-safety-profile-of-long-term-ayvakitayvakyt-avapritinib-treatment-at-2025-eha-and-eaaci-congresses-302480690.html

Blueprint Medicines Announces Data Reinforcing ... As previously presented,1 AYVAKIT demonstrated robust improvements through 144 weeks in overall symptom and symptom domain measures (skin, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03731260

NCT03731260 | (PIONEER) Study to Evaluate Efficacy and ... This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S221321982500491X

Continued symptom and quality of life improvement with ... With a median 2-year follow-up, once-daily avapritinib 25 mg demonstrated durable improvements in disease symptoms and quality of life with favorable longer- ...

5. ayvakithcp.com ayvakithcp.com/ism/efficacy/

PIONEER Trial Results for ISM Symptoms Patients treated with AYVAKIT + BSC saw milder symptoms at 24 weeks: 43% (58/134) reported a mild symptom burden (TSS <28) vs only 10% (14/139) at baseline.

6. blueprintmedicines.com blueprintmedicines.com/wp-content/uploads/2024/02/Blueprint-Medicines-Press-Release-AAAAI-2024-February-23-2024.pdf

Blueprint Medicines Highlights AYVAKIT® (avapritinib) ... -- AYVAKIT data in patients with indolent systemic mastocytosis show durable efficacy and favorable safety supporting long-term treatment ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8674139/

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