Rybrevant with Leclaza Shows Significantly Improved Progression-Free Survival vs. Tagrisso Treating EGFR-Mutated Advanced NSCLC

Image credit: Sebastian Kaulitzki | stock.adobe.com

The combination of Rybrevant (amivantamab-vmjw; Janssen Pharmaceutical) with Leclaza (lazertinib; Johnson & Johnson) produced significantly improved survival compared to Tagrisso (osimertinib; AstraZeneca) in the treatment of patients with previously untreated or Tagrisso-pretreated epidermal growth factor receptor (EGFR)–mutated advanced non–small-cell lung cancer (NSCLC). These findings from the Phase III MARIPOSA trial (NCT04487080) were published in The New England Journal of Medicine.¹

The majority of patients with EGFR-mutated advanced NSCLC show an initial response to third-generation EGFR-tyrosine kinase inhibitors (TKIs), however, real-world survival estimates demonstrate that 19% of patients are alive after five years, the authors noted.¹

“There is a continuous need to improve clinical outcomes with first-line treatment beyond those seen with EGFR-TKI monotherapy, given that 25% of patients die before receiving second-line therapy,” the study authors wrote.¹

Rybrevant is a bispecific antibody that targets EGFR and MET with immune cell-directing activity. The therapy is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy. It is also used as first-line treatment for patients with NSCLC in combination with chemotherapy (carboplatin-pemetrexed).² Leclaza is a highly selective, central nervous system–penetrant, third-generation EGFR-TKI that has shown efficacy in activating EGFR and p.Thr790Met (T790M) mutations.¹

“First-line [Rybrevant] plus chemotherapy and second-line [Rybrevant] monotherapy are approved for patients with EGFR exon 20 insertion–mutated advanced NSCLC. [Rybrevant]–chemotherapy has also significantly improved progression-free survival (PFS) as compared with chemotherapy in patients who had received [Tagrisso] for NSCLC,” the study authors wrote.¹

The international, randomized MARIPOSA trial enrolled 1074 patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. Patients were randomly assigned in a 2:2:1 ratio to receive Rybrevant with Leclaza (n=429) in an open-label fashion, Tagrisso (n=429) in a blinded fashion, or Leclaza in a blinded fashion (n=216) to evaluate how it contributes to the treatment components. The trial’s primary endpoint is PFS in the Rybrevant with Leclaza cohort as compared to the Tagrisso cohort, assessed by blinded independent central review.¹

Median PFS was significantly in favor of Rybrevant with Leclaza compared to Tagrisso, at 23.7 months compared to 16.6 months (hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). Rybrevant with Leclaza produced an objective response in 86% of patients (95% CI, 83 to 89) compared to 85% of patients (95% CI, 81 to 88) in the Tagrisso cohort.

Among 336 patients who achieved a confirmed response in the Rybrevant with Leclaza cohort and 314 who achieved a confirmed response in the Tagrisso cohort, median duration of response was 25.8 months with Rybrevant-Leclaza (95% CI, 20.1 to could not be estimated) compared to 16.8 months (95% CI, 14.8 to 18.5) in the Tagrisso cohort. An interim overall survival evaluation of the Rybrevant-Leclaza combination showed a hazard ratio for death of 0.80 (95% CI, 0.61 to 1.05) compared to Tagrisso.

In terms of safety, predominant adverse events (AEs) were EGFR-related toxic effects, with incidence of discontinuation for treatment-related AEs of 10% with the Rybrevant-Leclaza combination and 3% with Tagrisso.¹

“In the MARIPOSA trial, first-line treatment with [Rybrevant-Leclaza] significantly prolonged [PFS] as compared with Tagrisso monotherapy (hazard ratio for disease progression or death, 0.70; P<0.001),” the study authors wrote. “The [PFS] curves separated at 6 months and widened over time, according to the landmark analyses at 12, 18, and 24 months. With regard to [PFS], a benefit with [Rybrevant-Leclaza] was also observed across key prespecified subgroups, such as those defined according to a history of brain metastases.”¹

References

1. Cho B, et al. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med 2024, Published June 26, 2024 DOI: 10.1056/NEJMoa2403614.

2. Amivantamab-vmjw (Rybrevant) label. Janssen Biotech Inc. Accessed June 28, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761210s003lbl.pdf.