Tebentafusp (1) – Kimmtrak®

• Clinical trials
  • The pivotal study IMCgp100-202, hereinafter referred to as Study 202, is an ongoing, randomised, multicentre, controlled, open-label Phase II trial investigating the efficacy and safety of tebentafusp compared with treatment of the clinician’s choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A02:01-positive patients with untreated advanced or metastatic uveal melanoma.
  • The ongoing Study 102 is a single-arm Phase I/II trial investigating the efficacy and safety of tebentafusp in patients with advanced uveal melanoma.

Adults with inoperable or metastatic uveal melanoma who are HLA (human leukocyte antigen) A02:01-positive

• In summary, the additional benefit of tebentafusp is assessed as follows: a hint of a considerable additional benefit
• The G-BA identifies a considerable additional benefit of tebentafusp compared with a treatment of the clinician’s choice (dacarbazine, ipilimumab or pembrolizumab) in the treatment of HLA (human leukocyte antigen) A02:01-positive adults with inoperable or metastatic uveal melanoma.
• The level of evidence is classified as a hint.
• mortality
  • In Study 202, overall survival is defined as the time from the first day of randomisation to death from any cause.
  • For the endpoint of overall survival, there is a statistically significant difference in favour of tebentafusp compared with treatment according to the clinician’s choice (dacarbazine, ipilimumab or pembrolizumab).
  • The extent of the prolongation in overall survival achieved is considered a significant improvement.
  • Subgroup analyses for the overall survival endpoint reveal an interaction between treatment and the stratification variable LDH (≤ ULN vs. > ULN; p = 0.04). For the LDH ≤ ULN patient population, a statistically significant advantage was observed in favour of Tebentafusp. For the LDH > ULN patient population, no statistically significant advantage was observed.
• Morbidity – Symptoms (EORTC QLQ-C30)
  • Symptoms of the disease were assessed using the cancer-specific EORTC QLQ-C30 questionnaire.
  • In Study 202, response rates in the comparator arm were already below 70% at baseline, and the difference in response rates between the treatment arms was more than 15%. Therefore, the results are not used for the benefit assessment.
• Morbidity – Health status (EQ-5D, Visual Analogue Scale)
  • Health status was assessed in Study 202 using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • The results of the questionnaire were not taken into account due to the low response rates already observed at baseline and the significant differences in response rates between the groups.
• Health-related quality of life (EORTC QLQ-C30)
  • Health-related quality of life was assessed in Study 202 using the functional scales and the global health status scale of the EORTC QLQ-C30.
  • Due to the low response rates for the EORTC QLQ-C30, the results on health-related quality of life are not used for the benefit assessment.
• Side effects
  • Treatment-associated AEs (TEAEs) were evaluated from the day of the first study medication until 90 days after the last dose or the start of subsequent anti-tumour therapy.
  • For Study 202, the pharmaceutical manufacturer calculated the effect estimates – relative risk, odds ratio or risk difference – post hoc and presented them in the dossier. However, the differences in the duration of observation were not taken into account; consequently, the results were not used in the dossier assessment.
  • No statistically significant difference was observed for serious adverse events (SAEs).
  • Even with the supplementary data provided, time-to-event analyses and corresponding effect estimates are not available for all endpoints in the ‘side effects’ category. The analyses submitted therefore do not allow for a sufficiently reliable assessment and are thus not suitable for quantifying the extent of the additional benefit of Tebentafusp.
• Overall assessment
  • A statistically significant difference is observed for overall survival. The extent of the effect is assessed as a marked improvement.
  • In the endpoint category of morbidity and quality of life, the response rates for the EORTC QLQ-C30 and EQ-5D VAS assessment tools were already low at baseline and varied considerably between the groups. The results presented are therefore not usable.
  • With regard to side effects, appropriate analyses with effect estimates are not available for all endpoints. The analyses presented do not allow for a sufficiently reliable assessment and are therefore not suitable for quantifying the extent of the additional benefit of Tebentafusp.
  • In its overall assessment, the G-BA concludes that, due to the clear advantage in overall survival, there is an improvement in the treatment-related benefit for Tebentafusp within its therapeutic indication.

Courtesy translation only, please refer to the German original.