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 

-mutant non–small cell lung cancer (NSCLC).

CHRYSALIS-2 is the largest, single-cohort, prospective study of atypical 

-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.

, 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.

Videos

Byoung Chol Cho, MD, PhD, discusses findings from the CHRYSALIS-2 trial of amivantamab plus lazertinib in patients with atypical EGFR-mutant NSCLC.

Byoung Chul Cho, MD, PhD, professor, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, discusses key findings from the phase 3 MARIPOSA study (NCT04487080) of first-line amivantamab-vmjw (Rybrevant) plus lazertinib (Laclaza) vs osimertinib (Tagrisso) in 

-mutant locally advanced or metastatic non–small cell lung cancer (NSCLC).

The MARIPOSA study enrolled patients with treatment-naïve locally advanced or metastatic NSCLC with either 

 exon 19 deletions or L858R mutations. Patients were stratified by 

status. Patients were randomly assigned to receive the EGFR-MET bispecific antibody amivanatamab in combination with lazertinib, a CNS-penetrant, 3rd-generation EGFR TKI; osimertinib plus placebo; or lazertinib plus placebo.

The trial met its primary end point of improved progression-free survival (PFS) by blinded independent review with amivantamab plus lazertinib vs osimertinib, Cho begins. Median PFS with this combination was 23.7 months vs 16.6 months with osimertinib monotherapy, translating to a 30% reduction of the risk of progression or death. Unlike previous trials in 

-mutant lung cancer, the trial required serial brain MRIs for all patients, potentially leading to more frequent detection of progression, Cho notes. Accordingly, investigators measured extracranial PFS by BICR, and observed a 9-month improvement in median PFS with the amivantamab and lazertinib combination vs osimertinib monotherapy, he details. Additionally, time to second progression was notably enhanced with amivantamab plus lazertinib.

Although median overall survival (OS) was not estimable for both arms at the time of the analysis, Cho states that early interim OS data suggested a trend favoring the amivantamab combination over osimertinib, with a hazard ratio of 0.8 (

 = .11). This indicates the potential for improved survival outcomes with the combination therapy, he says.

Overall, the study establishes amivantamab plus lazertinib as a potential first-line standard of care for patients with 

-mutant advanced NSCLC, with significant improvements in PFS and a favorable safety profile, Cho concludes. 

Byoung Chul Cho, MD, PhD, discusses key findings from the phase 3 MARIPOSA study of first-line amivantamab plus lazertinib vs osimertinib  in EGFR-mutant locally advanced or metastatic  non– small cell lung cancer.

Byoung Chul Cho, MD, PhD

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

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