sBLA and NDA Submitted to FDA for Amivantamab and Lazertinib in EGFR-Mutant NSCLC

FDA

A supplemental biologics license application and new drug application seeking the approval of amivantamab-vmjw (Rybrevant) plus lazertinib as frontline therapy for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test, have been submitted to the FDA.¹

Both applications were based on data from the phase 3 MARIPOSA trial (NCT04487080) in which the combination of amivantamab and lazertinib led to a significant improvement in progression-free survival (PFS) vs osimertinib (Tagrisso) alone in patients with newly diagnosed advanced NSCLC with classical EGFR mutations.²

“The combination of [amivantamab] and lazertinib demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared to osimertinib in patients with previously untreated EGFR-mutated NSCLC. This remains an area of high unmet need as patients often experience treatment resistance and disease progression on currently available therapies,” Kiran Patel, MD, vice president, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine, stated in a news release.¹ “We believe this targeted, chemotherapy-free regimen may have the potential to transform the treatment of EGFR-mutated NSCLC, and we look forward to working with the FDA in review of these applications.”

MARIPOSA is a randomized phase 3 trial evaluating the EGFR- and MET-targeted bispecific antibody, amivantamab, plus the oral, third-generation EGFR TKI, lazertinib, vs osimertinib and lazertinib monotherapy.^1,3

PFS, the primary end point of the study, was evaluated using RECIST v1.1 criteria as assessed by blinded independent central review. Secondary end points include overall survival (OS), objective response rate (ORR), duration of response (DOR), second PFS (PFS2), and intracranial PFS.^1,3

Results from the trial, which were presented at the 2023 ESMO Congress with median follow-up of 22.0 months, demonstrated that the combination led to median PFS of 23.7 months (95% CI, 19.1-27.7) vs 16.6 months (95% CI, 14.8-18.5) with osimertinib alone (HR, 0.70; 95% CI, 0.58-0.85; P <.001). The 12- and 24-month PFS rates with the combination were 73% and 48%, respectively, vs 65% and 34% with osimertinib alone. Lazertinib monotherapy led to a median PFS of 18.5 months (95% CI, 14.8-20.1).²

Additionally, a 32% reduction in the risk of extracranial progression or death was seen with the combination vs osimertinib alone. Median extracranial PFS was 27.5 months (95% CI, 22.1-not evaluable [NE]) with the combination vs 18.5 months (95% CI, 16.5-20.3) with osimertinib alone (HR, 0.68; 95% CI, 0.56-0.83; P <.001). The 12- and 24-month extracranial PFS rates were 77% and 53% with the combination, respectively, vs 67% and 38% with osimertinib alone.

Interim OS, though not yet mature, showed a trend favoring the combination (HR, 0.80; 95% CI, 0.61-1.05; P =.11). The estimated 24-month PFS rates were 74% and 69% with the combination and osimertinib alone, respectively.

The ORR was 86% (95% CI, 83%-89%) with the combination vs 85% (95% CI, 81%-88%) with osimertinib alone. The combination also reduced the risk of second disease progression or death by 25% (HR, 0.75; 95% CI, 0.58-0.98; P =.03). At 24 months, 72% of patients in the combination arm remained free from second progression vs 64% in the osimertinib monotherapy arm.

Regarding safety, 75% of patients in the combination arm experienced grade 3 or greater adverse effects (AEs) vs 43% of those in the osimertinib arm. Serious AEs occurred in 49% and 33% of patients in the combination and monotherapy arms, respectively. AEs leading to death occurred in 8% and 7% of patients, respectively. Additionally, at least half as many patients in the combination arm vs the osimertinib arm experienced an AE leading to treatment interruption (83% vs 39% for the combination vs osimertinib, respectively), reduction (59% vs 5%), or discontinuation (35% vs 14%).

Frequently reported treatment-related AEs (TRAEs) in the combination arm included paronychia, rash, diarrhea, dermatitis acneiform, stomatitis, pruritus, hypoalbuminemia, peripheral edema, infusion-related reaction, alanine aminotransferase increase, constipation, aspartate aminotransferase increase, COVID-19, decreased appetite, anemia, nausea, hypocalcemia, and cough.

References

1. Johnson & Johnson submits supplemental biologics license application and new drug application to U.S. FDA seeking approval of RYBREVANT (amivantamab-vmjw) plus lazertinib for the treatment of patients with EGFR-mutated non-small cell lung cancer (NSCLC). News release. Johnson & Johnson. December 21, 2023. Accessed December 21, 2023. https://www.prnewswire.com/news-releases/johnson--johnson-submits-supplemental-biologics-license-application-and-new-drug-application-to-us-fda-seeking-approval-of-rybrevant-amivantamab-vmjw-plus-lazertinib-for-the-treatment-of-patients-with-egfr-mutated-non-small--302020967.html
2. Cho BC, Felip E, Spira AI, et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Ann Oncol. 2023;34(suppl 2):S1306. doi:10.1016/j.annonc.2023.10.062
3. A study of amivantamab and lazertinib combination therapy versus osimertinib in locally advanced or metastatic non-small cell lung cancer (MARIPOSA). ClinicalTrials.gov. Updated December 6, 2023. Accessed December 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04487080