ELCC 2024 Daily highlight 4

Dr Karolien Vekens, pulmonologist at the University Hospital Brussels discusses three amivantamab-related abstracts presented during the second mini oral session at ELCC 2024.

Amivantamab is an EGFR and MET directed bispecific antibody with immune cell-directing activity. In a first abstract, a post-progression analysis was presented of the phase III MARIPOSA-2 trial. In this study, the combination of amivantamab and chemotherapy with or without lazertinib was compared to chemotherapy alone in patients with EGFR-mutant metastatic NSCLC who progressed on or after osimertinib. Previously, this trial showed a significant benefit in progression-free survival (PFS) with amivantamab-chemotherapy vs. chemotherapy alone (HR[95%CI]: 0.48[0.36-0.64]). At ELCC 2024, it was shown that the addition of amivantamab to chemotherapy also led to a significantly longer time to treatment discontinuation (HR[95%CI]: 0.37[0.28-0.50]; p< 0.0001) and a delayed need for a subsequent line of therapy (HR[95%CI]: 0.37[0.28-0.50]; p< 0.0001). Finally, also the time to a second progression (PFS2) was markedly improved with amivantamab-chemotherapy vs. chemotherapy alone (HR[95%CI]: 0.60[0.40-0.92]; p= 0.017). The addition of amivantamab did come at the cost of a higher rate of hematological toxicity, but this was mainly limited to the 1^st treatment cycle.

In the phase III MARIPOSA trial, first line treatment with a combination of amivantamab and lazertinib was associated with a significant benefit in PFS compared to osimertinib in patients with EGFR-mutant metastatic NSCLC. About half of the patients treated with amivantamab-lazertinib in this trial required an amivantamab dose interruption during the first 4 months of therapy. Interestingly, however, data presented at ELCC 2024 show that the PFS of these patients was similar to the PFS of patients who did not have a dose interruption. As such, this analysis indicates that dose interruptions are an effective way to manage AEs in patients treated with amivantamab-lazertinib, without compromising the PFS.

The high rate of infusion-related reactions that is seen with amivantamab (>60%) formed the rationale to develop a subcutaneous (SC) formulation of this drug. In the phase 1B Paloma study, a four-weekly SC administration of amivantamab resulted in a similar drug exposure as the approved intravenous (IV) dose. Importantly, infusion related reactions were much less frequent (16%) and less severe than historic data with 2-weekly IV amivantamab. Another major advantage of the SC formulation consists of the very short administration time of only 7-10 minutes.

In conclusion, these three abstracts add to the body of evidence supporting the use of amivantamab in patients with EGFR-mutant metastatic NSCLC. However, many challenges remain to be tackled, including the optimal treatment sequence and the management of the toxicities that come with these regimens.