Frontline Amivantamab/Lazertinib Combo Shows Trend of OS Benefit in Advanced EGFR+ NSCLC

Shirish M. Gadgeel, MD

First-line amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) showed improved clinical outcomes compared with osimertinib (Tagrisso) in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC), with a promising trend toward overall survival (OS), according to a longer follow-up of the phase 3 MARIPOSA study (NCT04487080) presented at the 2024 IASLC World Conference on Lung Cancer.¹

Specifically, the median OS via blinded independent central review (BICR) based on RECIST v1.1 criteria for amivantamab/lazertinib was not estimable (NE; 95% CI, NE-NE) compared with 37.3 months (95% CI, 32.5-NE) for osimertinib (HR, 0.77; 95% CI, 0.61-0.96; P = .019). At 3 years, 61% of patients on the amivantamab-lazertinib remained alive vs 53% of those on the osimertinib arm.

“There was a trend in overall survival that favored amivantamab plus lazertinib. Median survival was not reached, whereas it was 37.3 months in patients treated with osimertinib,” Shirish M. Gadgeel, MD, division head for hematology/oncology at Henry Ford Health, said during an oral presentation of the longer follow-up.

In the primary analysis of MARISPOSA, which was at a median follow-up of 22.0 months, amivantamab/lazertinib showed a significant improvement in progression-free survival (PFS) via BICR compared with osimertinib (HR, 0.70; 95% CI, 0.58-0.85; P<.001). An early interim OS analysis demonstrated a favorable trend for amivantamab/lazertinib vs osimertinib (HR, 0.80; 95% CI, 0.61-1.05; P=.11).

In August 2024, the FDA approved amivantamab combined with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.² The approval was based on the primary MARISPOSA data.

In MARIPOSA, 1074 patients with treatment-naive, EGFR-mutated (with exon 19, exon 21, or L858R substitutions), locally advanced or metastatic NSCLC were randomly assigned 2:2:1 to open-label amivantamab plus lazertinib (n = 429), blinded osimertinib (n = 429), or blinded lazertinib (n = 216) to assess the contribution of components.

The primary end point was OS based on BICR via RECIST v1.1 criteria; secondary end points included time to treatment discontinuation (TTD), time to subsequent therapy (TTST), and PFS2 (after first subsequent therapy).

At a median follow-up of 31.1 months and a data cutoff date of May 13, 2024, 185 of 421patients (44%) and 145 of 428 patients (34%) remained on treatment of amivantamab-lazertinib and osimertinib, respectively. A total 155 patients and 233 patients from the respective arms were determined to have investigator-assessed progressive disease, therefore discontinuing treatment.

At the 31.1-month median follow-up of 31.1 months, the median intracranial duration of response (icDoR) was NE (95% CI, 21.4 months-NE) and 24.4 months (95% CI, 22.1-31.2) in the amivantamab/lazertinib and osimertinib arms, respectively. The intracranial overall response rate (icORR) was 77% in both arms; however, amivantamab/lazertinib (95% CI, 70%-83%) demonstrated greater durability of response with improved icDoR vs osimertinib (95% CI, 71%-83%).

The median TTD was 26.3 months (95% CI, 22.3-30.4) and 22.6 months (95% CI, 20.3-24.5) from the amivantamab/lazertinib and osimertinib arms, respectively.

Regarding TTST, the number of patients who experienced disease progression, discontinued treatment, and started subsequent therapy was similar between the 2 arms, at 72% with amivantamab/lazertinib and 74% with osimertinib. The median TTST was 30.0 months (95% CI, 20.3-36.0) with amivantamab/lazertinib and 24.0 months (95% Cim 22.5-20.2) with osimertinib (HR, 0.77; 95% CI, 0.65-0.93; P = .005). In both arms, the most common subsequent therapy after discontinuing study treatment was carboplatin/pemetrexed at 26% and 28%, respectively.

Additional findings showed that amivantamab/lazertinib significantly reduced the risk of second progression or death (PFS2) by 27%. The median PFS2 was NE (95% CI, 36.0-NE) and 32.4 months (95% CI, 29.3-NE) in the amivantamab/lazertinib and osimertinib arms, respectively (HR, 0.73; 95% CI, 0.59-0.91; P = .004). The 3-year landmark PFS2 rates were 57% and 49%, respectively.

“The MARIPOSA study is ongoing, and a prespecified final overall survival analysis with formal statistical testing will occur in the future. The FDA recently approved [the amivantamab/lazertinib] combination for the treatment of EGFR-mutant advanced non–small cell lung cancer for patients,” Gadgeel concluded.

References

1. 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.
2. 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 August 20, 2024. https://www.investor.jnj.com/news/news-details/2024/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/default.aspx