Dr Cho on Amivantamab Plus Lazertinib in Atypical EGFR-Mutated NSCLC

Byoung Chol Cho, MD, PhD, professor, internal medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, discusses efficacy and safety findings from the phase 1 CHRYSALIS-2 trial (NCT04077463) evaluating amivantamab-vmjw (Rybrevant) in combination with lazertinib (Leclaza) in patients with atypical EGFR-mutant non–small cell lung cancer (NSCLC).

CHRYSALIS-2 is the largest, single-cohort, prospective study of atypical EGFR-mutated advanced NSCLC, according to study investigators. Patients enrolled onto cohort C of the study were either treatment naive or had been exposed to no more than 2 prior lines of a TKI or chemotherapy. Notably, those harboring exon 20 insertions or exon 19 deletions/L858R co-mutations were excluded from this cohort.

At the 2024 ASCO Annual Meeting, data from the final analysis of cohort C demonstrated clinically meaningful and durable antitumor activity with the combination of amivantamab and lazertinib in patients who were treatment-naive or had experienced disease progression on afatinib, Cho begins. Among all patients in cohort C (n = 105), the combination therapy showed an objective response rate (ORR) of 52% (95% CI, 42%-62%), with a median duration of response (DOR) of 14.1 months (95% Ci, 9.5-26.2) and a median progression-free survival (PFS) of 11.1 months (95% CI, 7.8-17.8), he reports.

In the first-line setting (n = 49), the combination therapy produced an ORR of 57% (95% CI, 42%-71%) and a median DOR of 20.7 months (95% CI, 9.9-not evaluable [NE]), Cho states. At a median follow-up of 17.3 months (range, 0.1-31.5), the median PFS with the combination was 19.5 months (95% CI, 11.2-NE), which is notably longer than that reported with classical EGFR TKIs, he notes. In the second- and third-line settings (n = 56), the combination also demonstrated significant activity, Cho says. At a median follow-up of 15.4 months (range, 0.3-30.8), the ORR was 48% (95% CI, 35%-62%), the median DOR was 11.0 months (95% CI, 4.5-NE), and the median PFS was 7.8 months (95% CI, 5.4-11.1), he details.

The safety profile of amivantamab plus lazertinib was consistent with prior reports, with the most common adverse events (AEs) being primarily grade 1/2 EGFR- and MET-related toxicities, Cho continues. Rash and paronychia were the most frequently observed AEs, Cho adds.

These results indicate that the combination of amivantamab and lazertinib is effective not only as an initial treatment but also in the refractory setting, Cho concludes.