Avapritinib for Pediatric Solid Cancers

Not currently recruiting at 29 trial locations

Overseen By Lindsey Hoffman, DO

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Blueprint Medicines Corporation

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled cardiovascular disease, Seizure disorder, others

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

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: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests avapritinib, a new treatment for children with difficult-to-treat solid cancers, including some brain tumors. Researchers aim to determine if avapritinib is safe and effective for tumors with specific genetic changes. It suits children and teens with advanced cancers that have not responded to standard treatments and have certain genetic mutations. Participants will take the medication daily, and the trial will monitor its safety and effectiveness. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that participants cannot take certain drugs that strongly affect liver enzymes (CYP3A inhibitors or inducers) within 28 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that avapritinib is likely to be safe for children with solid tumors?

Research has shown that avapritinib has been used in patients for other conditions and is generally safe for long-term use, with most people not experiencing serious side effects. However, its safety and effectiveness for children remain unknown. This trial aims to determine its safety for young patients with certain solid tumors. Although this is the first time avapritinib is being tested in children for this purpose, its use in other conditions suggests it might be safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and radiation treatments for pediatric solid cancers, Avapritinib acts on a specific molecular target called KIT and PDGFRA mutations. This makes it unique because it directly interferes with the cancer cell growth pathways, potentially leading to more effective outcomes with fewer side effects. Researchers are excited about Avapritinib because it offers a targeted approach, which may provide better results for children who have not responded well to conventional therapies. Additionally, its oral administration provides a more convenient treatment option for young patients.

What evidence suggests that avapritinib might be an effective treatment for pediatric solid cancers?

Research has shown that avapritinib, the investigational treatment in this trial, may help treat certain childhood solid tumors with specific genetic changes. Early findings suggest it is generally safe for patients and has led to positive changes in some tumor scans. Notably, avapritinib targets a type of brain tumor called PDGFRA-altered high-grade glioma. While more information is still being gathered, these early results indicate that avapritinib could be a useful option for children with these difficult-to-treat cancers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged 2 to less than 18 with advanced solid tumors, including brain tumors that have specific genetic changes (mutations in KIT or PDGFRA) or a type of glioma called DMG-H3K27a. They should have tried standard treatments without success and not be eligible for other curative options. Participants need to be stable on certain medications, able to perform daily activities at least minimally, and agree to use contraception.

Inclusion Criteria

Participant agrees to utilize contraception consistent with local regulations.

My brain disease treatment with steroids has been stable or reduced for a week.

My diagnosis is DMG-H3K27a and standard treatments have not worked or are not available.

Exclusion Criteria

My platelet count is low and I haven't had a transfusion in the last 14 days.

Participant has International normalized ratio or prothrombin time (PT) > ULN.

My liver enzymes are high, but not over five times the normal limit if my cancer affects my liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation and Safety (Part 1)

Participants receive avapritinib to confirm dose, assess safety, and pharmacokinetics

28 days

4 visits (in-person)

Initial Efficacy and Safety (Part 2)

Participants receive avapritinib at the recommended dose to assess initial efficacy and safety

28 days

4 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

• Avapritinib

Trial Overview The study tests avapritinib, a medication targeting cancers with certain genetic mutations. It's an open-label trial where all participants receive the drug. The first part confirms the dose and assesses safety; the second part looks at how effective it is at a recommended dose while continuing safety assessments.

How Is the Trial Designed?

Group I: avapritinib Experimental Treatment 1 Intervention

Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 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+

Published Research Related to This Trial

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

The OncoKids panel is a next-generation sequencing assay that effectively detects various diagnostic, prognostic, and therapeutic markers in pediatric cancers, using only 20 ng of DNA and RNA from diverse sample types.

Validated on 192 clinical samples, the OncoKids panel demonstrated strong analytical sensitivity and reproducibility, supporting its use for routine clinical testing in a wide range of pediatric malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OncoKids: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies. Hiemenz, MC., Ostrow, DG., Busse, TM., et al.[2019]

Avapritinib is a selective tyrosine kinase inhibitor specifically targeting PDGFRA and KIT mutations, and it has been approved in the USA for treating gastrointestinal stromal tumors (GIST) with PDGFRA exon 18 mutations, including the D842V variant.

The drug is currently under regulatory review in the USA as a 4th-line treatment for GIST and is also being evaluated in the EU for the same indication, highlighting its potential as a significant treatment option for patients with advanced GIST.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avapritinib: First Approval. Dhillon, S.[2021]

Ceritinib, at a recommended dose of 500 mg/m2 once daily, demonstrated promising antitumor activity in pediatric patients with ALK-positive malignancies, particularly in inflammatory myofibroblastic tumors (IMT) and anaplastic large cell lymphoma (ALCL), as well as in some cases of neuroblastoma.

The safety profile of ceritinib was manageable, with 81% of patients experiencing grade 3 or 4 adverse events, primarily increases in liver enzymes, indicating that while the treatment can have serious side effects, it is consistent with what has been observed in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Fischer, M., Moreno, L., Ziegler, DS., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04773782

NCT04773782 | A Study of Avapritinib in Pediatric Patients ... This is a Phase 1/2, multicenter, open-label trial of avapritinib in participants 2 to < 18 years of age with advanced relapsed/refractory (R/R) solid ...

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. academic.oup.com academic.oup.com/neuro-oncology/article/24/Supplement_1/i37/6600616

A phase 1/2 study of avapritinib in pediatric patients with solid ... Prognosis for pediatric patients with advanced relapsed/refractory (R/R) solid (including central nervous system [CNS]) tumors is poor. KIT ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12065942/

Evaluation of the effectiveness and safety of avapritinib ... At the time of initiation of avapritinib, the majority of the patients were in good condition, with 52.4% having normal performance status ( ...

5. cell.com cell.com/cancer-cell/fulltext/S1535-6108(25)00070-4

Effective targeting of PDGFRA-altered high-grade glioma ... Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04773782?term=Avapritinib&viewType=Table&rank=7

A Study of Avapritinib in Pediatric Patients With Solid ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. catalogues.ema.europa.eu catalogues.ema.europa.eu/system/files/2024-03/BLU-285-1406%20PASS%20Protocol%20v5.0.pdf

POST-AUTHORISATION SAFETY STUDY (PASS) PROTOCOL Data will include: relevant baseline data at the time of the first dose of avapritinib and safety data from the time of the first dose of avapritinib to the ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/212608Orig1s013.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH 8.4 Pediatric Use. The safety and effectiveness of AYVAKIT in pediatric patients have not been established. 8.5 Geriatric Use. Of the 204 ...