Tagraxofusp (1) – Elzonris®

• Clinical trials
  • The study STML-401-0114, submitted for the benefit assessment, is a completed, multicentre, open-label, single-arm Phase I/II study (dose escalation and expansion) for the treatment of adults with blast-like plasmacytoid dendritic cell neoplasia (BPDCN) as first-line therapy or in relapsed/refractory cases, as well as for the treatment of adults with acute myeloid leukaemia using tagraxofusp.

Adults with blast-like plasmacytoid dendritic cell neoplasia (BPDCN)

• Hint for a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• Overall, a non-quantifiable additional benefit is identified for tagraxofusp in the treatment of patients with blast-like plasmacytoid dendritic cell neoplasia, as the scientific evidence does not permit quantification.
• Overall, there is a hint of a non-quantifiable additional benefit for tagraxofusp, as the scientific evidence does not permit quantification.
• mortality
  • In the STML-401-0114 study, the endpoint of overall survival was defined as the time from the first Tagraxofusp infusion to death from any cause.
  • As no comparative data are available, no conclusions can be drawn regarding the extent of the additional benefit.
• morbidity
  • The clinical presentation of BPDCN is accompanied by externally visible, often painful and/or itchy skin lesions, which represent a burden for the affected patient.
  • However, information is lacking regarding the (evidence-based) basis for the weighting factors used for the type of skin lesion (patches, plaques, tumours) as well as on inter-rater reliability; consequently, questions remain regarding the reliable assessment of the intensity of the lesion and the proportion of the body affected.
  • There is therefore, on the one hand, doubt as to whether the mSWAT measurement tool used to assess skin response is sufficiently valid and reliable to reflect the cutaneous burden of disease and, on the other hand, whether strictly objective measurements were available in this regard in the present study.
  • Overall, the dossier does not contain any adequate aggregated results for the mSWAT, which is why no results relating to the mSWAT can be presented.
  • PFS was assessed as a secondary endpoint in the STML-401-0114 study and defined as the time from the start of treatment with tagraxofusp until the occurrence of progression and/or death from any cause, whichever occurred first.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • The assessment of the morbidity component ‘disease progression’ in the bone marrow, peripheral blood, lymph nodes, spleen and liver compartments was carried out, in accordance with the operationalisation, not on the basis of symptoms but using imaging procedures and laboratory parameters. Consequently, the assessment of disease progression in these areas is deemed not to be directly relevant to patients.
  • For the reasons stated, whilst the PFS endpoint is reported, it is not taken into account in this assessment.
  • Notwithstanding this, no conclusions can be drawn regarding the extent of the additional benefit, as no comparative data are available.
  • The endpoint ‘complete remission’ (CR/CRc) was the primary efficacy endpoint for stage 3 in first-line therapy in the STML-401-0114 study and included patients achieving complete remission (CR) and complete remission with minimal residual skin abnormality (CRc).
  • Complete remission (CR), defined as the disappearance of all signs of the disease in all compartments, may, in the context of the indicated therapeutic indication, generally be an important prognostic factor and relevant to treatment decisions.
  • Overall, there are doubts regarding the validity of the endpoint for assessing patient-relevant therapeutic effects; the complete remission endpoint (CR/CRc) is presented merely as supplementary information.
  • Notwithstanding this, no conclusions can be drawn regarding the extent of the additional benefit, as no comparative data are available.
  • In the STML-401-0114 study, the stem cell transplant (SCT) rate was defined as the number and proportion of patients who were eligible for an SCT and who received one.
  • The endpoint ‘stem cell transplantation rate’ is therefore presented for supplementary information only.
  • As no comparative data are available, no conclusions can be drawn regarding the extent of the additional benefit.
  • In the overall assessment of the morbidity data, no conclusions can be drawn regarding the extent of the additional benefit.
• quality of life
  • No data on quality of life were collected.
• Side effects
  • Adverse events were defined as any adverse medical events occurring from the first administration of Tagraxofusp up to 30 days after the last infusion, regardless of their relationship to the study medication.
  • All patients enrolled in the study experienced at least one adverse event.
  • An adverse event of CTCAE grade ≥ 3 occurred in 22 (75.9%) patients in stages 1–3 of the STML-401-0114 study and in 9 (69.2%) patients in phase 3.
  • A serious adverse event occurred in 12 (41.4 %) patients in phases 1–3 and in 4 (30.8 %) patients in phase 3.
  • One patient (3.4%) in stages 1–3 and one patient (7.7%) in stage 3 experienced an adverse event that led to discontinuation of the study medication.
  • AE of particular clinical interest occurred in nearly 80% of study participants in the SMQ ‘medicinal product-induced liver disorders’.
  • An overall analysis of the results on side effects does not allow any conclusions to be drawn regarding the extent of the additional benefit, as no comparative data are available.
• Overall assessment
  • The benefit assessment of tagraxofusp for first-line treatment of patients with blast-like plasmacytoid dendritic cell neoplasia is based on the STML-401-0114 study, which provides results on mortality, morbidity and side effects.
  • Due to the single-arm design of the STML-401-0114 study, no data are available for a comparative assessment.
  • It is therefore not possible to quantify the additional benefit on the basis of the data provided.
  • Overall, Tagraxofusp is found to provide a non-quantifiable additional benefit for the treatment of patients with blast-like plasmacytoid dendritic cell neoplasia, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.