FDA Approves Amivantamab-Vmjw and Lazertinib for First-Line Treatment of NSCLC

The FDA has approved amivantamab-vmjw (Rybrevant; Johnson & Johnson) plus lazertinib (Lazcluze; Johnson & Johnson) for the first line treatment of adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 18 deletion or exon 21 L858R substitution mutations. This approval marks the first and only multi-targeted chemotherapy-free regimen that demonstrated superiority compared with osimertinib for this patient population.¹

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"This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long," Jill Feldman, co-founder of the EGFR Resisters, a patient advocacy group, said in the news release. "Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I'm thrilled that more patients can now experience the progression-free survival benefits seen in the MARIPOSA study."¹

The MARIPOSA (NCT04487080) study is a phase 3, international, randomized trial evaluating the efficacy of amivantamab and lazertinib compared with osimertinib for patients with EGFR mutation or Exon 21 L858R substitution positive, locally advanced or metastatic NSCLC, according to the clinical trial information. The study consisted of 3 parts, with a screening phase, a treatment phase, and a follow-up phase. The primary end point was progression-free survival (PFS) of the combination compared with osimertinib. Secondary endpoints included overall survival, objective response rate (ORR), duration of response (DOR), PFS after first subsequent therapy, time to symptomatic progression, intracranial PFS, and incidence and severity of adverse events (AEs).^2,3

Investigators included those with newly diagnosed disease that was treatment naïve and not amendable to curative therapy, including surgical resection and chemoradiation, and at least 1 measurable lesion that was not previously irradiated. Patients were excluded if they had any prior systemic treatment at any time for locally advanced stage III or metastatic stage IV or had an active or past history of leptomeningeal disease, brain metastases, or interstitial lung disease/pneumonitis. In the combination arm, patients received amivantamab in 28-day cycles, once weekly in cycle 1 and then every 2 weeks subsequent cycles. Lazertinib was administered orally once daily. In the comparator arm, patients received osimertinib orally once daily with a matching placebo of lazertinib orally once daily. In the third arm, patients received lazertinib orally once daily and a matching placebo of osimertinib orally once daily.²

There were 1074 patients included, with 429 to the combination group, 429 to the osimertinib group, and 216 to the lazertinib group. The median PFS was 23.7 months compared with 16.6 months for the combination and osimertinib groups, respectively. The ORR was 86% and 85%, respectively. Of patients with a confirmed response (336 in the combination group and 314 in the osimertinib group), the median DOR was 25.8 months and 16.8 months, respectively.³

For safety, investigators reported that discontinuation due to treatment-related AEs was 10% in the amivantamab and lazertinib group and 3% in the osimertinib group.³

"The unique combination of Rybrevant and Lazcluze demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC as shown with the MARIPOSA study," Alexander Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute, said in the news release. "Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex."¹

REFERENCES

1. Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) approved in the US as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed August 20, 2024. https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-us-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer-302226047.html#:~:text=RARITAN%2C%20N.J.%2C%20Aug.%2020,non-small%20cell%20lung%20cancer%20

2. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). ClinicalTrials.gov identification: NCT04487080. Updated August 12, 2024. Accessed August 20, 2024. https://www.clinicaltrials.gov/study/NCT04487080

3. Cho BC, Lu S, Felip E, et al. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. Published online June 26, 2024. doi:10.1056/NEJMoa2403614