Cemiplimab (5) – Libtayo®

• Clinical trials
  • The EMPOWER-Lung 3 trial is an ongoing, double-blind, randomised, controlled Phase III trial comparing cemiplimab plus platinum-based chemotherapy with placebo plus platinum-based chemotherapy, which is being conducted at 74 trial centres in Europe and Asia.
  • The KEYNOTE 024 trial is an open-label, randomised, controlled Phase III trial comparing pembrolizumab with platinum-based combination chemotherapy, which was conducted from 2014 to 2016 at 142 trial centres in North America, Europe and Australia/New Zealand.
  • The KEYNOTE 042 trial is an open-label, randomised, controlled Phase IIItrial comparing pembrolizumab with a combination of carboplatin and either paclitaxel or pemetrexed, which was conducted from 2014 to 2022 at 196 trial centres in North and South America, Asia and Eastern Europe.
  • The KEYNOTE 189 trial is an ongoing, double-blind, randomised, controlled Phase IIIstudy comparing pembrolizumab plus platinum-based chemotherapy with platinum-based chemotherapy alone, which is being conducted at 143 study centres, including in Europe and North America.
  • The KEYNOTE 407 trial is an ongoing, double-blind, randomised, controlled Phase IIIstudy comparing pembrolizumab plus carboplatin-based chemotherapy with carboplatin-based chemotherapy alone, being conducted at 125 study centres, including in Europe, North America and Asia.

a) Adults with locally advanced or metastatic NSCLC with PD-L1 expression ≥ 50% and no EGFR, ALK or ROS1 aberrations; first-line treatment

• An additional benefit is not proven.
• Overall, no additional benefit has been demonstrated for cemiplimab in combination with platinum-based chemotherapy compared with the appropriate comparator therapy for adults with locally advanced or metastatic NSCLC with PD-L1 expression ≥ 50 % and no EGFR, No proof of ALK or ROS1 aberrations.
• Overall review
  • When forming the relevant patient populations from the KEYNOTE trials, the pharmaceutical manufacturer only included in the adjusted indirect comparison the results of those patients for whom, according to a retrospective survey, carboplatin represented a suitable treatment option.
  • Significant proportions of the study populations in the KEYNOTE trials were therefore not included in the analyses. No such restriction of the populations was applied to the EMPOWER-Lung 3 trial.
  • There are therefore significant uncertainties regarding the comparability of the study populations between the studies presented, meaning that the indirect comparisons are not suitable for benefit assessment.

b) Adults with locally advanced or metastatic NSCLC with PD-L1 expression of ≥ 1 % to < 50 % and no EGFR, ALK or ROS1 aberrations; first-line treatment

• The additional benefit is not proven.
• Overall, there is no evidence of additional benefit for cemiplimab in combination with platinum-based chemotherapy compared with the appropriate comparator therapy for adults with locally advanced or metastatic NSCLC with PD-L1 expression of ≥ 1 % to < 50 % and no EGFR, There is no proof of ALK or ROS1 aberrations.
• Overall review
  • When forming the relevant patient populations from the KEYNOTE trials, the pharmaceutical manufacturer only included in the adjusted indirect comparison the results of those patients for whom, according to a retrospective survey, carboplatin represented a suitable treatment option.
  • Relevant proportions of the study populations in the KEYNOTE trials were therefore not included in the analyses. No such restriction of the populations was applied to the EMPOWER-Lung 3 trial.
  • Furthermore, the submitted analyses include a significant proportion of patients with PD-L1 expression < 1 per cent, who – given the marketing authorisation for cemiplimab in combination with platinum-based chemotherapy – are not the subject of the assessment.
  • There are therefore significant uncertainties regarding the comparability of the study populations between the studies presented, meaning that the indirect comparisons are not suitable for benefit assessment.

Courtesy translation only, please refer to the German original.