The Janssen Pharmaceutical Companies of Johnson & Johnson announced positive results from the Phase 3 MARIPOSA study, revealing that RYBREVANT® (amivantamab-vmjw) combined with lazertinib significantly improved progression-free survival (PFS) compared to osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or L858R substitution mutations. The study's findings, presented at the European Society for Medical Oncology (ESMO) 2023 Congress, highlight the potential of this combination therapy to become a new standard of care in the first-line treatment of EGFR-mutated NSCLC.
Key Findings from the MARIPOSA Study
The MARIPOSA study (NCT04487080) enrolled 1,074 patients and compared RYBREVANT® plus lazertinib against osimertinib and lazertinib alone. The primary endpoint, PFS, demonstrated a statistically significant and clinically meaningful improvement in the combination arm. At a median follow-up of 22 months, the median PFS for RYBREVANT® and lazertinib was 23.7 months, compared to 16.6 months for osimertinib (HR=0.70; 95% CI, 0.58–0.85; P<0.001). This represents a 30% reduction in the risk of disease progression or death.
Byoung Chul Cho, M.D., Ph.D., from Yonsei Cancer Center, noted, "With the combination of RYBREVANT and lazertinib in the MARIPOSA study, progression-free survival was significantly improved in patients with previously untreated EGFR-mutated NSCLC compared to osimertinib."
Secondary Endpoints and Subgroup Analysis
Secondary endpoints, including overall survival (OS), objective response rate (ORR), and duration of response (DOR), also favored the RYBREVANT® and lazertinib combination. An interim OS analysis showed a favorable trend (HR=0.80; 95% CI, 0.61–1.05; P=0.11), with ongoing monitoring to determine statistical significance. The median DOR was significantly longer for patients receiving the combination, with a nine-month improvement (25.8 vs. 16.8 months).
Consistent benefits were observed across prespecified patient subgroups, including those with and without brain metastases. In patients with a history of brain metastases, the median PFS was 18.3 months with the combination versus 13.0 months with osimertinib alone (HR, 0.69; 95% CI, 0.53-0.92).
Safety and Tolerability
The safety profile of the RYBREVANT® and lazertinib combination was consistent with the known profiles of the individual treatments. Grade 3 or higher treatment-related adverse events (AEs) were more frequent in the combination arm (75%) compared to the osimertinib arm (43%). However, toxicity was manageable with dose interruptions, reductions, and supportive care. Common AEs included rash, paronychia, hypoalbuminemia, and peripheral edema. The rate of interstitial lung disease (ILD) was low (less than 3%) in both arms.
Implications for Clinical Practice
The MARIPOSA study suggests that the combination of RYBREVANT® and lazertinib could offer a more effective first-line treatment option for patients with EGFR-mutated NSCLC. Peter Lebowitz, M.D., Ph.D., from Janssen Research & Development, stated, "The prolonged duration of progression-free survival and favorable trend in overall survival observed in the MARIPOSA study show the potential of RYBREVANT in combination with lazertinib to transform first-line treatment in EGFR-mutated NSCLC."
Janssen plans to submit these results to health authorities for potential regulatory approval, which could establish a new treatment paradigm for this patient population.
