Amivantamab/Lazertinib Show OS Improvement for mNSCLC Over Osimertinib

Results from the phase 3 MARIPOSA trial found that amivantamab plus lazertinib met the final pre-specified secondary end point of overall survival in NSCLC.

Amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) demonstrated clinically meaningful and statistically significant improvement in overall survival (OS) over the standard-of-care (SOC) osimertinib (Tagrisso) as a first-line therapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R mutations, according to a news release from the drug’s developer Johnson & Johnson.¹

Results from the final OS analysis of the phase 3 MARIPOSA trial (NCT04487080), which is reported to be presented at an upcoming major medical meeting, build upon data from the interim analysis previously presented at the IASLC 2024 World Conference on Lung Cancer (WCLC).² At the data cutoff date of May 13, 2024, median OS via blinded independent review (BICR) for amivantamab/lazertinib was not estimable (NE; 95% CI, NE-NE) vs 37.3 months (95% CI, 32.5-NE) with osimertinib (HR, 0.77; 95% CI, 0.61-0.96; P = .019). Furthermore, 3-year survival was 61% and 53% in each respective arm.

Additionally, at a median follow-up of 22.0 months, the combination therapy displayed a statistically significant progression-free survival (PFS) benefit via BICR vs osimertinib (HR, 0.70; 95% CI, 0.58-0.85; P < .001).A favorable trend for the combination therapy was demonstrated over osimertinib in an early interim OS analysis (HR, 0.80; 95% CI, 0.61-1.05; P = .11).

The FDA previously approved amivantamab plus lazertinib as a frontline therapy for those with locally advanced or metastatic EGFR-mutated NSCLC in August 2024.³

"The combination of these 2 agents previously demonstrated an improvement in progression-free survival, but this does not always capture the impact on the entire treatment course. Evaluation of overall survival can better demonstrate the benefit of a first-line treatment regimen," Stephen Liu, MD, associate professor of medicine at Georgetown University School of Medicine and director of Thoracic Oncology and head of Developmental Therapeutics at Georgetown's Lombardi Comprehensive Cancer Center, said in the news release.¹ "Seeing this increase in OS in a trial with mature data is powerful and reaffirms that first-line treatment with [amivantamab] and [lazertinib] can lead to better patient outcomes."

After screening 1375 patients between November 2020 and May 2022, 1074 patients were randomized 2:2:1 to receive either amivantamab/lazertinib (n = 429), osimertinib (n = 429), or lazertinib monotherapy (n = 216). A weekly dose of 1050 mg intravenous amivantamab, increased to 1400 mg for patients 80 kg or greater, was administered for 4 weeks, encompassing 1 cycle. The initial infusion was split over 2 days––350 mg on day 1 cycle 1 and the remainder on day 2 cycle 1––and subsequent cycles included the same amivantamab dose administered every 2 weeks. Osimertinib and lazertinib were taken once daily orally, at 80 mg and 240 mg, respectively.

In the combination and SOC groups, the median age was 64 (range, 25-88) and 63 (range, 28-88), respectively, with most patients being female (64% vs 59%) between both arms. Both groups were predominantly Asian (58% vs 59%) or White (38% vs 38%), and the median body weight in respective groups was 62.5 kg (range, 32-118) and 62 kg (range, 35-109).

Furthermore, most patients in each respective group had an ECOG performance status score of 1 (67% vs 65%) and were never smokers (70% vs 69%). The most common histology in both arms was adenocarcinoma (97% vs 97%), and most patients had exon 19 deletions (60% vs 60%).

The primary end point of the trial was progression-free survival (PFS) by blinded independent central review (BICR). Secondary end points included OS, objective response rate, duration of response, and safety.

Safety data previously published in The New England Journal of Medicine, found that grade 3 or higher adverse events (AEs) occurred in 75% of the combination arm and 43% of the SOC arm at the data cutoff point of August 11, 2023.⁴ Furthermore, 8% and 7% of respective arms had AEs leading to death. AEs resulting in dose interruption, reduction, or discontinuation occurred in 83%, 59%, and 35% of the amivantamab/lazertinib arm and 39%, 5%, and 14% of the osimertinib arm.

References

1. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) show statistically significant and clinically meaningful improvement in overall survival versus osimertinib. Press release. Johnson & Johnson. January 7, 2025. Accessed January 7, 2025. https://tinyurl.com/yj5xyxtr
2. Gadgeel S, Cho BC, Lu S, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced NSCLC: longer follow-up of the MARIPOSA study. Presented at: IASLC 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA02.03.
3. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed January 7, 2025. https://tinyurl.com/yxc8u8t4
4. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. doi:10.1056/NEJMoa2403614