Epcoritamab (1) – Tepkinly®

• Clinical trials
  • The GCT3013-01 trial is a single-arm, ongoing Phase I/II trial in adults with various forms of relapsed/refractory (r/r) B-cell lymphoma.

Adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following at least two lines of systemic therapy

• In summary, the additional benefit of epcoritamab is assessed as follows: a hint of a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Overall, with regard to the strength of the evidence, there is a hint of a non-quantifiable additional benefit.
• mortality
  • Of 139 patients, 55.4% had died by the data cut-off date of 21 April 2023.
  • It is not possible to interpret or evaluate the mortality data due to the lack of a control group. Consequently, no conclusions regarding the extent of the additional benefit can be drawn for the mortality category.
• Morbidity – Progression-free survival (PFS)
  • In the GCT3013-01 study, PFS was assessed as a secondary endpoint. PFS was defined as the period from Day 1 of the first treatment cycle until the date of disease progression or death from any cause, whichever occurred first.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint. The overall conclusion regarding the extent of the additional benefit remains unaffected by this, as there is no control group and no conclusion regarding the extent of the additional benefit can be drawn. The PFS endpoint is presented for supplementary information.
• Morbidity – Tumour response
  • The primary efficacy endpoint ‘Overall response rate (ORR)’ is defined as the proportion of patients who achieve either a complete response (CR) or a partial response (PR) as their best response, based on the IRC assessment according to the Lugano criteria.
  • Response is not assessed on the basis of symptoms, but primarily on the basis of imaging procedures within the framework of the Lugano classification and LYRIC. For this reason, the above-mentioned endpoints are classified as not patient-relevant.
  • A complete response, combined with a reduction in disease symptoms that is perceptible to the individual, is, in principle, patient-relevant for the benefit assessment. However, the operationalisation presented here is based primarily on imaging procedures. No further details on physical examinations are provided in the study documentation, nor are they taken into account in the Lugano Classification or LYRIC. Complete response does not constitute a validated surrogate for a patient-relevant endpoint in the population covered by the therapeutic indication. Overall, the endpoint of complete response is therefore assessed as not being patient-relevant.
  • Notwithstanding this, no conclusions regarding the extent of the additional benefit can be drawn from the results of the GCT3013-01 study on the tumour response endpoint, as there is no control group. The overall response rate endpoint is presented for supplementary information.
• Morbidity – Health status
  • General health status was assessed in the GCT3013-01 study using the visual analogue scale (VAS) of the EQ-5D.
  • The results for general health status showed response rates of < 60 % at all post-baseline assessment time points. Against this background, no evaluable data are available for the endpoint of general health status.
  • Nevertheless, no conclusions regarding the extent of the additional benefit can be drawn from the results of the GCT3013-01 study on health status, as there is no control group.
• Health-related quality of life
  • Data on health-related quality of life were collected in the GCT3013-01 study using the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) questionnaire.
  • The FACT-Lym results showed response rates of < 60 % at all post-baseline assessment time points.
  • Against this background, no evaluable data on health-related quality of life are available.
  • Nevertheless, no conclusions regarding the extent of the additional benefit can be drawn from the results of the GCT3013-01 study on health-related quality of life, as there is no control group.
• Side effects – Total adverse events (AEs)
  • An adverse event occurred in almost all patients (138 out of 139 patients (99.3 %)). These are presented here for supplementary information only.
• Side effects – Serious adverse events (SAEs)
  • At least one serious adverse event occurred in 95 out of 139 patients (68.3%).
• Side effects – Severe adverse events (CTCAE grade ≥ 3)
  • At least one severe AE with a CTCAE grade of ≥ 3 occurred in 96 out of 139 patients (69.1%).
• Side effects – Therapy discontinuation due to adverse events
  • In 22 patients (15.8%), an adverse event occurred that led to discontinuation of the study medication.
• Side effects – Specific AEs
  • Serious adverse events with an incidence of ≥ 10 % of patients by system organ class (SOC) included immune system disorders (28.8 %) and infections and parasitic diseases (29.5 %).
  • Severe adverse events of CTCAE grade ≥ 3 with an incidence of ≥ 10% of patients, by system organ class (SOC), were disorders of the blood and lymphatic system (29.5%), infections and parasitic disorders (25.2 per cent) and investigations (13.7 per cent).
  • An adverse event with an incidence of ≥ 10 % of the patients occurred: cytokine release syndrome (CRS), which occurred as an adverse event (regardless of severity) in 49.6% of patients and as a serious adverse event in 28.8% of patients.
  • In summary, no conclusions can be drawn regarding the extent of the additional benefit for the ‘side effects’ category, as there is no control group.
• Overall assessment
  • The data available for the benefit assessment come from the single-arm GCT3013-01 study, which formed the basis for marketing authorisation. No further data are available, nor is there any indirect comparison.
  • As no comparative data are available, no conclusion can be drawn regarding the extent of the additional benefit on the basis of these results.
  • In summary, the available results are classified as non-quantifiable in their overall assessment, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.