As reported in the Journal of Clinical Oncology by Tomasini et al, findings in a cohort of the early-phase CHRYSALIS-2 trial indicate activity of amivantamab plus lazertinib in patients with atypical EGFR-mutated advanced non–small cell lung cancer (NSCLC).
Study Details
In the international trial, 105 patients in the cohort (cohort C) received (as of January 2024) amivantamab at 1,050 mg (1,400 mg if body weight was ≥ 80 kg) once weekly for the first 4 weeks and then once every 2 weeks plus lazertinib at 240 mg once daily. Patients with solitary exon 20 insertions or coexisting exon 20 insertions or exon 19 deletions/L858R EGFR mutations were excluded from the study. Overall, 68% of patients were Asian. A total of 49 patients had received no prior treatment in the advanced setting; among 56 patients with prior treatment, 88% had received EGFR tyrosine kinase inhibitors. The primary endpoint was investigator-assessed objective response rate.
Key Findings
The most common atypical EGFR mutations were G719X (56%), L861X (26%), and S768X (23%), including single and compound mutations. Median follow-up was 16.1 months (range = 0.1–31.5 months).
Objective responses (all partial) were observed in 55 patients (52%, 95% confidence interval [CI] = 42%–62%). Median duration of response was 14.1 months (95% CI = 9.5–26.2 months). An additional 35% of patients had stable disease. Median progression-free survival was 11.1 months (95% CI = 7.8–17.8 months); median overall survival was not estimable (95% CI = 22.8 months to not estimable).
Among treatment-naive patients, the objective response rate was 57% (95% CI = 42%–71%), median response duration was 20.7 months (95% CI = 9.9 months to not estimable), and median progression-free survival was 19.5 months (95% CI = 11.2 months to not estimable). Among previously treated patients, the objective response rate was 48% (95% CI = 35%–62%), median response duration was 11.0 months (95% CI = 4.5 months to not estimable), and median progression-free survival was 7.8 months (95% CI = 5.4–11.1 months).
Grade ≥ 3 adverse events occurred in 70% of patients who received the doublet, most commonly rash (13%), pneumonia (10%), pulmonary embolism (8%), and hypoalbuminemia (8%). Serious adverse events occurred in 50% of patients. Adverse events led to discontinuation of any study treatment in 28% of patients, with treatment-related discontinuation occurring in 7%. One treatment-related death was reported.
The investigators concluded: “In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.”
Pascale Tomasini, MD, of Aix Marseille University–CNRS, INSERM, CRCM, Hȏpital de La Timone, Marseille, France, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Janssen Research & Development. For full disclosures of all study authors, visit ascopubs.org.
