RYBREVANT (amivantamab) - Non-small cell lung cancer (NSCLC)

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 = 0.395 (95% CI = [0.296; 0.528]; p < 0.0001), in a phase 3, randomised, open-label study;
• a progression-free survival median of 11.4 months (95% CI = [9.79; 13.70]) in the amivantamab + carboplatin + pemetrexed (ACP) group and 6.7 months (95% CI = [5.59; 7.33]) in the carboplatin + pemetrexed(CP) group;
• the objective response rate assessed by an IRC of 73.0% (95% CI = [65.2; 79.9]) in the ACP group and 47.4% (95% CI = [39.2; 55.6]) in the CP group with an OR = 2.97 (95% CI = [1.84; 4.79]; 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 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;
• an excess short-term mortality (first 8 months);
• the absence of data on brain metastases, with a possible heterogeneity of effect depending on their presence, and with no interaction test;
• the absence of any robust conclusion that can be drawn based on the quality of life findings;
• 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 90% and 42% of patients respectively;

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