KEY TAKEAWAYS
- The MARIPOSA phase 3 trial aimed to compare 1L Ami + Laz with Osi in patients with EGFR-mutant NSCLC.
- Researchers noticed that Ami + Laz offers a significant advancement as a standard of treatment for patients with EGFR-mutant advanced NSCLC.
Imivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant, 3rd-generation EGFR TKI. In MARIPOSA, first-line (1L) ami+laz provided a statistically significant improvement in progression-free survival (PFS) vs osimertinib (osi) in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) (HR, 0.70; P< 0.001), including in patients with a history of brain metastases (HR, 0.69; Cho AnnOncol 2023;34, LBA14). Patients with TP53co-mutations, detectable circulating tumor DNA (ctDNA), and baseline brain or liver metastases have poor prognoses.
Enriqueta Felip and the team aimed to evaluate outcomes for patients in these high-risk subgroups from MARIPOSA.
They performed an inclusive analysis within the MARIPOSA trial, which enrolled patients with treatment-naïve, EGFR-mutant (Ex19del or L858R) advanced NSCLC. This analysis included patients randomized to ami+laz (n = 429) or osi (n = 429). Pathogenic alterations were analyzed by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood were analyzed at baseline and Cycle (C) 3 Day (D) 1 with Biodesix droplet digital PCR (ddPCR).
The baseline ctDNA for NGS analysis of pathogenic alterations was available for 636 patients (ami+laz, n = 320; osi, n = 316). Among patients with TP53 co-mutation, median progression-free survival (mPFS) was 18.2 months (mo) for ami+laz vs 12.9 mo for osi (HR, 0.65; P= 0.003). Patients with TP53 wild-type had a trend favoring ami+laz for mPFS (HR, 0.75; P =0.11). In patients with ddPCR-detectable ctDNA at baseline, ami+laz significantly prolonged mPFS vs osi (20.3 vs 14.8 mo; HR, 0.68; P= 0.002).
Further, ami+laz significantly improved mPFS vs osi in patients with ctDNA clearance at C3D1 (24.0 vs 16.5 mo; HR, 0.64; P= 0.004) and in patients who did not clear ctDNA (16.5 vs 9.1 mo; HR, 0.48; P= 0.014). For patients with liver metastases at baseline, ami+laz significantly prolonged mPFS vs osi (18.2 vs 11.0 mo; HR, 0.58; P= 0.017), which is consistent with the improved PFS for ami+laz vs osi in patients with a history of brain metastases.
The study concluded that Ami + Laz showed significantly improved mPFS compared to Osi in patients with biomarkers of high-risk disease. Given the prevalence of these features in up to 85% of patients, Ami + Laz emerges as a crucial new standard of care for treatment-naïve EGFR-mutant advanced NSCLC.
The trial was sponsored by Janssen Research & Development, LLC.
Source: https://meetings.asco.org/abstracts-presentations/232880
Clinical Trial: https://clinicaltrials.gov/study/NCT04487080
Felip E, Cho B.C., Gutiérrez V, et al. (2024). “Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 16; abstr 8504), 10.1200/JCO.2024.42.16_suppl.8504
