Researchers revealed follow-up results from the Phase Ib/II CHRYSALIS-2 study cohort evaluating the safety and tolerability of the combination of amivantamab-vmjw, a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), plus platinum-based chemotherapy (carboplatin and pemetrexed) in patients with relapsed/refractory non-small cell lung cancer (NSCLC) and EGFR mutations. These findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Congress on Lung Cancer (WCLC).
"Often, patients with EGFR-mutated NSCLC develop resistance to treatment during the course of therapy. Resistance in patients is typically diverse and polyclonal, meaning their tumors can have more than one type of resistance caused by different pathways. These variables can make their disease much harder to control and treat with targeted therapy alone," said Se-Hoon Lee, MD, PhD, Professor of Medicine at the Samsung Medical Center and Sungkyunkwan University School of Medicine and presenting author.
"These long-term follow-up data from the CHRYSALIS-2 study in patients with previously treated EGFR-mutated NSCLC demonstrate the importance of treatment strategies that combine chemotherapy with targeted therapy to better address complex resistance patterns after treatment with third-generation EGFR TKIs."
CHRYSALIS-2 (NCT04077463) is an ongoing, multicohort, clinical study evaluating amivantamab-vmjw in combination with lazertinib in patients with advanced NSCLC with EGFR exon 19 deletion mutations (ex19del) or L858R activating mutations. One cohort of CHRYSALIS-2 evaluated the combination of amivantamab-vmjw and lazertinib with platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC who experienced disease progression on EGFR TKIs, a regimen similar to the one being evaluated in the ongoing MARIPOSA-2 study.
Results from the amivantamab-vmjw, lazertinib, and chemotherapy combination cohort (n=20) were featured in a mini oral presentation (Abstract MA13.06) at the IASLC 2023 WCLC. Enrolled patients received a median of two prior lines of therapy. Prior therapies included osimertinib (70%) and first- and second-generation EGFR TKIs (45%).
The combination of amivantamab-vmjw and lazertinib with chemotherapy yielded an objective response rate of 50 percent, with 11 out of 20 patients remaining on treatment. Median duration of response was not reached after a median follow-up of 13.1 months. Median progression-free survival (PFS) was 14 months. Eight of 10 responders had a response duration of at least 6 months. Five patients were treated beyond progression, with a median incremental treatment duration of 4.2 months. The most common treatment-emergent adverse events included low white blood cell count (neutropenia; 90%), rash (75%), and infusion-related reactions (65%).
About the CHRYSALIS-2 Study
CHRYSALIS-2 (NCT04077463) is an open-label Phase I/Ib study to evaluate the safety and pharmacokinetics of lazertinib, a third-generation EGFR-TKI, as monotherapy or in combination with amivantamab-vmjw, a human bispecific EGFR, and c-MET antibody in participants with advanced NSCLC. The study enrolled 460 patients with advanced NSCLC.
Amivantamab-vmjw received accelerated approval by the FDA in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The NCCN Clinical Practice Guidelines in Oncology for Non-Small Cell Lung Cancer prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC