Rybrevant plus chemotherapy improved response and delayed illness development for sufferers with EGFR-mutated lung most cancers after Tagrisso remedy.
Amongst sufferers with EGFR-mutated non–small cell lung most cancers (NSCLC), Rybrevant (amivantamab-vmjw) plus chemotherapy improved efficacy in contrast with chemotherapy alone in keeping with outcomes from the section 3 MARIPOSA-2 trial assessing Tagrisso (osimertinib) resistance mechanisms, as introduced on the 2025 American Society of Medical Oncology Annual Assembly.
The idea of the MARIPOSA-2 trial was to evaluate the efficacy and security of Rybrevant plus chemotherapy with or with out Lazcluze (lazertinib) for sufferers with EGFR-mutated NSCLC after illness development on or after Tagrisso.
For sufferers with detectable ctDNA at baseline, the median progression-free survival (PFS) within the Rybrevant/chemotherapy group (104 sufferers) was 5.9 months versus 4.2 months within the chemotherapy alone arm (195 sufferers). The target response price (ORR) was 67% versus 39%, respectively.
For sufferers who have been EGFR/MET impartial, the median PFS was 5.6 months within the Rybrevant arm (39 sufferers) versus 3.9 months within the chemotherapy arm (41 sufferers). The ORR was 64% versus 37% between each arms, respectively.
For sufferers who have been EGFR/MET-dependent, the median PFS was 5.5 months within the Rybrevant arm (27 sufferers) versus 4.1 months within the chemotherapy arm (62 sufferers). The ORR between both arm was 70% versus 35%.
For these with unknown resistance mechanisms, the median PFS was 9.7 months within the Rybrevant arm (38 sufferers) versus 4.2 months within the chemotherapy arm (92 sufferers). The ORR was 68% versus 43%, respectively.
For sufferers who had a MET amplification, the median PFS was 4.4 months within the Rybrevant arm (12 sufferers) versus 3.1 months within the chemotherapy arm (30 sufferers). The ORR was 67% versus 23%, respectively.
In sufferers with secondary EGFR mutations, the median PFS was 5.7 months within the Rybrevant arm (15 sufferers) versus 5 months within the chemotherapy arm (39 sufferers). The ORR was 73% versus 44%, respectively.
“Rybrevant/chemotherapy improved median PFS and ORR versus chemotherapy throughout baseline subgroups, together with these related to identified or unknown mechanisms, as recognized with ctDNA NGS [next generation sequencing] evaluation,” Dr. Raffaele Califano, a advisor in medical oncology at The Christie and College Hospital of South Manchester, and co-authors wrote within the poster. “Rybrevant/chemotherapy was efficacious no matter the kind of Tagrisso resistance mechanism.”
The trial randomly assigned 657 sufferers 2:2:1 to both Rybrevant/Lazcluze (263 sufferers), chemotherapy (263 sufferers), or Rybrevant/chemotherapy (131 sufferers). The main target of the presentation was within the Rybrevant/chemotherapy and chemotherapy alone arms.
Sufferers have been eligible for remedy if that they had regionally superior or metastatic NSCLC, documented EGFR exon 19 deletion or L858R substitutions, progressed on or after Tagrisso monotherapy, and had an ECOG efficiency rating of 0 or 1.
Resistance mechanisms that have been analyzed included TP53 co-mutation, MET amplification, secondary EGFR mutations, EGFR/MET impartial, EGFR/MET dependent, or unknown.
The diagnostic check was ctDNA NGS. Blood samples have been collected at baseline, the evaluation of the ctDNA was carried out with Guardant 360 CDx or PredicineCARE NGS assay, adopted by blood samples collected once more on the finish of remedy.
Reference:
“Amivantamab plus chemotherapy versus chemotherapy in EGFR-mutant superior NSCLC after illness development on Tagrisso: Outcomes by Tagrisso resistance mechanisms in MARIPOSA-2” by Dr. Raffaele Califano, et al., introduced on the 2025 American Society of Medical Oncology Annual Assembly.
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