A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling

NCT04773782 | Completed Phase 1 FDA Drug

• 1 other identifier: BLU-285-3101
• Study Type: interventional
• Target: 29
• Locations: 8 countries
• Sites: 24

Brief Summary

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 tumors, including central nervous system (CNS) tumors, that harbor a PDGFRA and/or KIT mutation (including non-synonymous point mutations, insertions, and deletions) or amplification, or DMG-H3K27a who have no available curative treatment options. This is a single-arm trial in which all participants will receive avapritinib. The study consists of 2 parts: dose confirmation, safety, and PK (Part 1) and initial efficacy, safety, and PK at the Part 2 recommended dose (Part 2).

Conditions

Solid Tumor, Unspecified, Child; Relapsed Solid Neoplasm; CNS Tumor

Keywords

KIT; PDGFRA; Relapsed/Refractory Solid Tumor; Glioma; H3K27M; DMG-H3K27a

Outcome Measures

Primary Outcomes (3)

• Determination of recommended Part 2 dose (Part 1)

  up to 8 months

• Objective Response Rate (Part 2)

  up to 36 months

• Rate and severity of adverse events (Part 1)

  up to 8 months

Secondary Outcomes (13)

• Objective Response Rate (Part 1 and Part 2)

  up to 42 months

• Rate and severity of adverse events (Part 1 and Part 2)

  up to 42 months

• Palatability assessments as measured by the 5-point Hedonic scale (Part 1 and Part 2)

  up to 42 months

• Duration of Response (Part 1 and Part 2)

  up to 42 months

• Progression-free survival (Part 1 and Part 2)

  up to 42 months

Study Arms (1)

avapritinib

EXPERIMENTAL

Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles.

Drug: avapritinib

Interventions

avapritinib DRUG

oral administration

Also known as: BLU-285

avapritinib

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant must be 2 to \< 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor.
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion.
• b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (\< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines.

You may not qualify if:

• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count \< 75 × 10\^9/L (\< 100 × 10\^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) \< 1.0 × 10\^9/L.
• Hemoglobin \< 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT \> 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT \> 5 × ULN for age.
• Total bilirubin \> 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin \> 3 × ULN or direct bilirubin \> 1.5 × ULN.
• Serum creatinine \> 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) \> ULN (\> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF \> 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (\> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.

Sponsors & Collaborators

• Blueprint Medicines Corporation: lead

Study Sites (26)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of California San Francisco, Benioff Children's Hospital

San Francisco, California, 94518, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Sydney Children's Hospital, Kids Cancer Center

Sydney, New South Wales, 2031, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Medizinische Universitat Wein

Vienna, Vienna, 1090, Austria

Location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsmedizin Göttingen

Göttingen, Lower Saxony, 37075, Germany

Location

Hopp Children's Cancer Center

Heidelberg, Germany

Location

Dipartimento di Oncologia Medica ed Ematologia - S.C. Pediatria Oncologica

Milan, 20133, Italy

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medial Center

Seoul, 06351, South Korea

Location

Great Ormond Street Hospital For Children

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Recurrence; Glioma

Interventions

avapritinib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 26, 2021
• Study Start: February 24, 2022
• Primary Completion: November 21, 2025
• Study Completion: November 21, 2025
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); AU (1); DE (2); KR (2); US (15); IT (1); GB (1); CA (1)