RYBREVANT (amivantamab) - cell lung cancer (NSCLC) - (Exon 19 deletions or Exon 21)

The clinical benefit of RYBREVANT 350 mg (amivantamab) concentrate for solution for infusion is substantial in the MA indication.

Considering:

• evidence of the superiority of RYBREVANT (amivantamab) in combination with carboplatin and pemetrexed compared to the carboplatin and pemetrexed combination on progression-free survival assessed by an independent review committee (IRC), with an HR = 0.48 (95% CI = [0.36; 0.64]; p < 0.0001), in a phase 3, randomised, open-label study;
• a progression-free survival median of 6.3 months (95% CI = [5.55; 8.41]) in the amivantamab + carboplatin + pemetrexed (ACP) group and 4.2 months (95% CI = [4.04; 4.44]) in the carboplatin + pemetrexed(CP) group;
• the objective response rate assessed by an IRC of 63.8% (95% CI = [55.0; 72.1]) in the ACP group and 36.2% (95% CI = [30.3; 42.3]) in the CP group with an OR = 3.10 (95% CI = [2.00; 4.80]; p < 0.0001);
• the modest relevance of the effect size measured on the progression-free survival median and of the objective response rate;

and despite:

• the open-label design of the study;
• the significant amendments having been made to the hypotheses of the MARIPOSA-2 trial and, in particular, concerning the combination of interest and the dosage, with selection during the trial of only one combination of interest;
• the beneficial effect on progression-free survival primarily due to a reduction in progressions, whereas progression-free deaths were increased, with no test comparing the cumulative incidences of progression-free deaths between the treatment groups;
• the lack of evidence of an impact on overall survival compared to chemotherapy, on the basis of currently available data;
• the absence of any robust conclusion that can be drawn based on the quality of life findings;
• a possible attrition bias related to the number of untreated subjects (7.6% of patients included in the CP group, versus 0.8% in the ACP group) and consent withdrawals (11.0% of patients included in the CP group, versus 4.6% in the ACP group);
• the safety profile marked by a high frequency of grade ≥ 3 adverse events, serious adverse events and adverse events having led to permanent discontinuation of at least one study treatment, as well as by the occurrence of:
  • dermatological reactions (in particular rashes) and infusion-related reactions in 71% and 59% of patients respectively,
  • venous thromboembolic events in 10% of patients;

The Committee deems that RYBREVANT 350 mg (amivantamab) concentrate for solution for infusion, in combination with carboplatin and pemetrexed chemotherapy, provides a minor clinical added value (CAV IV) compared to carboplatin and pemetrexed chemotherapy.