Talquetamab (1) – Talvey®

• Clinical trials
  • To assess the additional benefit of talquetamab in the therapeutic indication of relapsed and refractory multiple myeloma (≥ 3 prior treatments), the pharmaceutical manufacturer submitted data from the single-arm, open-label Phase I/II MonumenTAL-1 trial as part of the dossier.

Adults with relapsed and refractory multiple myeloma who have previously received at least three lines of treatment, including an immunomodulatory active ingredient (INN), a proteasome inhibitor and an anti-CD38 antibody, and who have shown disease progression during their most recent treatment

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Consequently, the certainty of the evidence is assessed as a hint.
• mortality
  • The endpoint of overall survival is defined in the MonumenTAL-1 study as the time from the first dose of talquetamab until death from any cause.
  • At the data cut-off date relevant for the benefit assessment, 81 people (28.1 %) in the non-TCRDT pre-treated cohort had died.
  • In the TCRDT-pretreated cohort, 14 individuals (45.2%) had died.
  • The median survival had not yet been reached in either cohort at the time of the data cut-off.
  • Due to the single-arm study design, a comparative analysis of the overall survival data is not possible.
• Morbidity – Progression-free survival (PFS)
  • In the MonumenTAL-1 study, PFS is defined as the period between the date of the first administration of talquetamab and the date of the first documented disease progression according to the IMWG criteria based on laboratory parameters as well as haematological and imaging procedures, or death from any cause, whichever occurs first.
  • The median PFS was 9.56 months in the cohort not previously treated with TCRDT and 5.03 months in the cohort previously treated with TCRDT.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint.
  • Due to the single-arm study design, a comparative assessment of the PFS data is not possible.
• Morbidity – Overall Response Rate (ORR)
  • The overall response rate is the primary endpoint in the MonumenTAL-1 study and is defined as the achievement of a partial response or better, as assessed by an independent review committee using the IMWG criteria.
  • The overall response rate was 72.9% in the cohort not previously treated with TCRDT and 58.1% in the cohort previously treated with TCRDT.
  • The overall response rate is presented here as a supplementary primary endpoint of the study.
  • Due to the single-arm study design, a comparative evaluation of the data on the overall response rate is not possible.
• Morbidity – EQ-5D-VAS
  • General health status was assessed in Phase II of the MonumenTAL-1 study using the European Quality of Life – 5 Dimensions (EQ-5D-VAS) visual analogue scale.
  • The response rate for the EQ-5D-VAS was already less than 70% as early as cycle 1, day 1, in cohorts A, B and C; consequently, the analyses presented are not considered suitable for benefit assessment.
  • Furthermore, no analyses could be identified for the cohort pre-treated with TCRDT.
  • Nevertheless, a comparative assessment of the EQ-5D-VAS data is not possible due to the single-arm study design.
• Morbidity – symptom scales of the EORTC-QLQ-C30
  • Symptoms were assessed in the MonumenTAL-1 study using the symptom scales of the EORTC-QLQ-C30 in N = 122 patients in Cohort A and N = 109 patients in Cohort C.
  • As part of the commenting procedure, the pharmaceutical manufacturer provided analyses of the MMRM results for the EORTC-QLQ-C30 for the aggregated cohort of patients not previously treated with TCRDT (N = 231) and for the cohort of patients previously treated with TCRDT (N = 19), each for the final cycle, with a response rate of > 70 per cent.
  • For the aggregated cohort of patients with non-TCRDT prior treatment, the analyses for cycle 3, day 1 are used here.
• quality of life
  • Quality of life was assessed in the MonumenTAL-1 study using the functional scales of the EORTC-QLQ-C30 in N = 122 patients in Cohort A and N = 109 patients in Cohort C.
  • As part of the commenting procedure, the pharmaceutical manufacturer provided analyses of the MMRM assessments for the EORTC QLQ-C30 were submitted for the aggregated data of the non-TCRDT pre-treated cohort (N = 231) and the TCRDT pre-treated cohort (N = 19), in each case for the final cycle with a response rate of > 70 per cent.
  • For the aggregated cohort of patients with non-TCRDT prior treatment, the analyses for cycle 3, day 1 are used here.
  • The analyses of the EORTC-QLQ-C30 functional scales for Cycle 1, Day 1, for the cohort previously treated with TCRDT are not included.
• Side effects
  • In the MonumenTAL-1 study, at least one adverse event (AE) occurred in all patients in both the non-TCRDT-pretreated and TCRDT-pretreated cohorts.
  • Severe AEs occurred in 77.8% of the non-TCRDT pre-treated cohort and in 96.8% of the TCRDT pre-treated cohort.
  • Serious AEs occurred in 50.7% of the non-TCRDT pre-treated cohort and in 61.3% of the TCRDT pre-treated cohort.
  • An AE leading to discontinuation of the study medication occurred in 6.6% of the cohort not pre-treated with TCRDT and in 6.5% of the cohort pre-treated with TCRDT.
  • A comparative assessment of side effects is not possible due to the single-arm study design.
• Overall assessment
  • Data for the benefit assessment are available from the single-arm, multicentre Phase I/II MonumenTAL-1 trial, which formed the basis for marketing authorisation.
  • The pharmaceutical manufacturer has submitted data on mortality, morbidity, quality of life and side effects relating to the MonumenTAL-1 study.
  • However, due to the single-arm study design, these data do not allow for a comparative assessment.
  • Overall, 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.