MARIPOSA update: Amivantamab-lazertinib bests osimertinib for EGFRm NSCLC at 3 years

The updated efficacy analysis of the phase III MARIPOSA trial continues to favour amivantamab plus lazertinib over osimertinib for first-line (1L) treatment of patients with EGFR-mutant (EGFRm) advanced non-small cell lung cancer (NSCLC).

There was a strong overall survival (OS) trend after a median follow-up of 31.1 months (median not estimable [NE] vs 37.3 months; hazard ratio [HR], 0.77; p=0.019). [WCLC 2024, abstract OA02.03]

“The OS curves separated early and widened over time, favouring amivantamab plus lazertinib. Sixty-one percent of patients receiving amivantamab plus lazertinib were alive at 3 years vs 53 percent for osimertinib,” said Dr Shirish Gadgeel from the Henry Ford Cancer Institute/Henry Ford Health, Detroit, Michigan, US, at WCLC 2024.

Intracranial efficacy

The amivantamab-containing regimen showed a favourable trend in intracranial progression-free survival (PFS) with sustained and durable central nervous system control at 3 years vs osimertinib (median 24.9 vs 22.2 months; HR, 0.82; p=0.165). The landmark intracranial PFS was twofold greater with the former vs the latter (38 percent vs 18 percent).

Over half of the participants in the amivantamab arm had an intracranial response at year 3; there were none in the osimertinib arm. Intracranial objective response rates were identical between the amivantamab and osimertinib arms (77 percent for both), but the former showed longer intracranial durability of response than the latter (median NE vs 24.4 months).

Post-progression outcomes

Compared with the comparator regimen, the investigational combination also showed significantly longer time to treatment discontinuation (26.3 vs 22.6 months; HR, 0.80; p=0.014) and time to subsequent therapy (30 vs 24 months; HR, 0.77; p=0.005). These outcomes translated to more participants in the investigational arm remaining on treatment (40 percent vs 29 percent) and starting subsequent therapy (45 percent vs 32 percent) at 3 years.

There were similar fractions of combination and osimertinib recipients who progressed, discontinued treatment, and went on to receive subsequent treatment (72 percent vs 74 percent). Most of the participants who discontinued study treatment received second-line therapy, the most common being doublet chemotherapy in both arms (41 percent and 45 percent).

The combination regimen also reduced the risk of second disease progression or death by 27 percent compared with osimertinib (median PFS2 NE vs 32.4 months; HR, 0.73; p=0.004). The landmark PFS2 was 57 percent with the combo regimen and 49 percent with osimertinib.

Aligns with prior findings

Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity, while lazertinib is a third-generation EGFR tyrosine kinase inhibitor. [Mol Cancer Ther 2020;19:2044-2056; J Thorac Oncol 2022;17:558-567]

In MARIPOSA, 1,074 patients with treatment-naïve, EGFRm (Exon 19 deletions or Exon 21 L858R mutations) locally advanced or metastatic NSCLC were randomized 2:2:1 to open-label amivantamab-lazertinib, blinded osimertinib, or blinded lazertinib. The lazertinib monotherapy arm was included to evaluate the contribution of components.

The current findings build on previously reported MARIPOSA data showing the PFS and OS benefit of the combo regimen as opposed to osimertinib in this patient setting. [N Engl J Med 2024;doi:10.1056/NEJMoa2403614] Based on these results, the US FDA gave their nod on the amivantamab plus lazertinib combination for 1L treatment of patients with common EGFRm advanced NSCLC. [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer, accessed September 30, 2024]

“[In this updated analysis,] amivantamab plus lazertinib continues to show a trend towards improved OS while also improving post-progression outcomes vs osimertinib, reaffirming [the role of the combo regimen] as 1L standard-of-care for EGFRm advanced NSCLC,” said Gadgeel.

“Amivantamab plus lazertinib … is improving long-term outcomes vs osimertinib based on its multitargeted mechanism and blocking of EGFR and MET with immune cell-directing activity,” he continued.

As this is an ongoing trial, Gadgeel noted that a prespecified final OS analysis with formal statistical testing shall be conducted in the future.