sBLA Submitted for Amivantamab/Lazertinib for Locally Advanced/Metastatic NSCLC

The median progression-free survival (PFS) per blinded independent central review was 23.7 months in the amivantamab plus lazertinib arm compared with 16.6 months in the osimertinib arm at a median follow-up of 22 months. Clinically meaningful benefit was observed in the experimental arm across prespecified patient subgroups. This included groups based on race, EGFR mutation status, brain metastases history, and performance status.

A supplemental biologics license application (sBLA) has been submitted alongside a new drug application for amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) as a potential treatment for patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 19 deletions or L858R substitution mutations, according to a press release from Johnson & Johnson.¹

The application is supported by data from the phase 3 MARIPOSA study (NCT04487080), the results of which were presented at the 2023 European Society for Medical Oncology Congress (ESMO).² Results from the study indicated that first-line amivantamab and lazertinib resulted in a 30% decrease in the risk of progression or death vs osimertinib (Tagrisso; HR, 0.70; 95% CI, 0.58-0.85; P <.001).

A positive trend towards overall survival was also reported in the experimental arm compared with the control arm at the first interim analysis per blinded independent central review (HR, 0.80; 95% CI, 0.61-1.05; P = .11).

“The combination of [amivantamab] and lazertinib demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared [with] 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 of clinical development, Solid Tumors, at Johnson & Johnson Innovative Medicine, said in the press 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.”

The median progression-free survival (PFS) per blinded independent central review was of 23.7 months in the amivantamab plus lazertinib arm compared with 16.6 months in the osimertinib arm at a median follow-up of 22 months. Clinically meaningful benefit was observed in the experimental arm across prespecified patient subgroups. This included groups based on race, EGFR mutation status, brain metastases history, and performance status.

“Despite advances in EGFR-mutated NSCLC treatment, novel targeted therapies and regimens are needed to address resistance and disease progression, which are nearly inevitable with current treatments,” presenting author Byoung Chul Cho, MD, PhD, a medical oncologist and professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, South Korea, said at the time of the data readout.²

“With the combination of [amivantamab] and lazertinib in the MARIPOSA study, progression-free survival was significantly improved in patients with previously untreated EGFR-mutated NSCLC compared to osimertinib. These results support the potential of this [amivantamab] combination to be a future standard of care.”

Most adverse effects (AEs) associated with amivantamab/lazertinib were low-grade and were manageable with dose reductions and interruptions. The most common grade 3 or higher AEs were rash and paronychia. Additionally, the experimental arm had higher rates of EGFR- and MET-related AEs such as hypoalbuminemia and peripheral edema, as well as venous thromboembolism.

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 22, 2023. http://tinyurl.com/kjpr73d5
2. Landmark phase 3 MARIPOSA study shows RYBREVANT® (amivantamab-vmjw) plus lazertinib resulted in 30 percent reduction in risk of disease progression or death compared to osimertinib in patients with EGFR-mutated non-small cell lung cancer. News release. Janssen Pharmaceutical Companies of Johnson & Johnson. October 23, 2023. Accessed December 22, 2023. https://bit.ly/3RM0oSM