Observational study evaluating the long-term safety and efficacy of avapritinib in the first-line treatment of patients with platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumour (GIST)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  AYVAKYT
• Study drug International non-proprietary name (INN) or common name:
  AVAPRITINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01EX18) avapritinib

  avapritinib
• Medical condition to be studied:
  Gastrointestinal stromal tumour
• Additional medical condition(s):
  Platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumour (GIST)

Population studied

• Age groups:
  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  50

Study design details

• Main study objective:
  The overall objective is to collect long-term safety and efficacy data for avapritinib in first-line patients with PDGFRA D842V-mutated GIST, (or following ≤4 months of imatinib treatment).
• Outcomes:
  To describe types, severity and rates of AEs, SAEs, AEs leading to discontinuation or decreased dosing of avapritinib, AESIs, and deaths. This PASS has been implemented following a commitment to the EMA to address the Specific Obligation of the CMA in Europe to provide additional safety data for patients with PDGFRA D842V-mutated GIST on first-line avapritinib treatment, (or≤4 months of imatinib), To evaluate efficacy in terms of disease response to treatment, PFS and OS as well as duration of treatment and duration of response.
• Data analysis plan:
  Analyses will be performed on the safety population, i.e. enrolled patients who received at least one dose of avapritinib. For the primary endpoint, the number, proportions and incidence rate of patients experiencing an AE (overall and by SOC/PT terms), and the number, proportions of patients with avapritinib treatment changes due to an AE (overall and by comorbidity) will be determined. For the secondary endpoints, the following will be determined: 1) overall survival (OS), progression-free survival, treatment duration, tumour response and response duration by the Kaplan-Meier method, 2) OS rates at 12- and 24-months, and 3) overall response rates. Inviting consecutive patients at sites and retrospective patients who discontinued treatment will minimize selection bias. A statistical analysis plan will be developed before the first data lock point, which will detail handling of missing data, correction of inconsistencies or errors, and differences in outcome definitions.