Avapritinib (2) – Ayvakyt®

• Clinical trials
  • The ongoing pivotal PATHFINDER trial is an uncontrolled Phase II trial.
  • The ongoing EXPLORER supportive study is an uncontrolled Phase I study with a Phase II expansion.

Adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasia (SM-AHN) or mast cell leukaemia (MCL) following at least one course of systemic therapy

• Hint for a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• Overall, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.
• As a comparative assessment is therefore not possible, the strength of the evidence is rated as a hint.
• mortality
  • Overall survival was defined in the PATHFINDER and EXPLORER studies as the period from the first administration of study medication until death from any cause.
  • The median survival time had not yet been reached in either study at the time of data cut-off.
  • Due to the single-arm study design, a comparative assessment of the results regarding overall survival is not possible.
  • The effect of avapritinib on mortality cannot be conclusively assessed on the basis of the data presented.
• Morbidity – Complete remission (CR)
  • The operationalisation of the response criteria is based almost exclusively on laboratory parameters and histological findings.
  • Whilst response is assessed almost exclusively on the basis of laboratory parameters and histological findings, morbidity is not primarily assessed on the basis of disease symptoms, but rather on the basis of asymptomatic findings that are not directly relevant to the patient.
• Morbidity – Patient Global Impression of Symptom Severity (PGIS)
  • The mean PGIS score (range: 0–4) at baseline is 2.5 at the pooled level and 1.5 in cycle 3.
  • Due to the single-arm study design, a comparative assessment of the PGIS data is not possible.
• Morbidity – Symptoms (EORTC QLQ-C30)
  • Symptoms of the disease were assessed in the PATHFINDER and EXPLORER studies using the symptom scales of the EORTC QLQ-C30 questionnaire.
  • Due to the single-arm study design, a comparative assessment of the EORTC QLQ-C30 data is not possible.
• Health-related quality of life (EORTC-QLQ-C30)
  • Health-related quality of life was assessed in the PATHFINDER and EXPLORER studies using the functional scales and the global scale for general health status of the EORTC-QLQ-C30 questionnaire.
  • Due to the single-arm study design, it is not possible to carry out a comparative analysis of the data on the EORTC-QLQ-C30.
• Side effects
  • Adverse events occurred in all patients in both studies.
  • Adverse events (AEs) of CTCAE grade ≥ 3 were documented in 72% of patients in the PATHFINDER study (n = 67) and in 75% in the EXPLORER study (n = 12).
  • Serious adverse events (SAEs) were reported in approximately 40% of treated patients in the PATHFINDER study (n = 67) and in just under 42% of treated patients in the EXPLORER study (n = 12).
  • Cognitive effects and intracranial haemorrhages were specified as AESI.
  • Due to the single-arm study design, a comparative assessment of the data on side effects is not possible.
• Overall assessment
  • This benefit assessment is based on the results of the pivotal Phase II PATHFINDER trial and the supportive Phase I/II EXPLORER trial regarding mortality, morbidity, health-related quality of life and side effects.
  • Due to the single-arm study design, a comparative assessment of the data on avapritinib is not possible.
  • The indirect comparison of overall survival presented in the context of the BLU-285-2405 study is subject to major uncertainties.
  • Overall, the indirect comparisons presented are not suitable for drawing conclusions about the extent of the additional benefit.
• Overall assessment
  • In the overall assessment, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.