Data suggests that the combo of  RYBREVANT + chemotherapy led to a statistically significant and clinically meaningful reduction in mortality compared to TAGRISSO in participants with previously untreated EGFR-mutant advanced NSCLC. In some EGFR-mutant lung cancers, TAGRISSO initially works but eventually fails due to resistance caused by MET amplification or new EGFR mutations. Overcoming this resistance is key to maintaining treatment effectiveness. RYBREVANT targets both EGFR and MET, and when combined with chemotherapy, it helps restore treatment response and improve outcomes, as seen in the MARIPOSA-2 trial.

The basis of the MARIPOSA-2 trial was to assess the efficacy and safety of RYBREVANT + chemotherapy with or without LAZCLUZE (lazertinib) for patients with EGFR-mutated NSCLC after disease progression on or after TAGRISSO. For patients who were EGFR/MET dependent, the median PFS was 5.5 months in the RYBREVANT arm and 4.1 months in the chemotherapy-alone arm. The Objective Response Rate (ORR) was 70% and 35%, respectively. For those with unknown resistance mechanisms, the median PFS was 9.7 months in the RYBREVANT arm and 4.2 months in the chemotherapy-alone arm. The ORR was 68% and 43%, respectively. For patients with a MET amplification, the median PFS was 4.4 months in the RYBREVANT arm and 3.1 months in the chemotherapy-alone arm. The ORR was 67% and 23%, respectively. 

In patients with secondary EGFR mutations, the median PFS was 5.7 months in the amivantamab arm vs. 5 months in the chemotherapy arm. The ORR was 73% vs. 44%, respectively. The RYBREVANT arm showed positive outcomes in the patients when compared with chemotherapy alone. The biggest challenge of RYBREVANT has been its toxicity.

KOL insights

“Amivantamab/chemotherapy improved median PFS and ORR vs. chemotherapy across baseline subgroups, including those associated with known or unknown mechanisms, as identified with ctDNA NGS [next-generation sequencing] analysis. Amivantamab/chemotherapy was efficacious regardless of the type of osimertinib resistance mechanism.” – Expert Opinion.

“This is an analysis of the progression-free survival stratified by molecular aberration, which represents the mechanism of resistance post-osimertinib in all patients who were enrolled in the MARIPOSA-2 study. The data show that chemotherapy plus amivantamab is an effective regimen, regardless of the baseline mechanism of resistance post-[osimertinib], and therefore it remains a standard of care in this setting.” – Expert Opinion.

Conclusion

In EGFR-mutated NSCLC, where TAGRISSO is the industry leader with nearly USD 6 billion annually sales, Johnson & Johnson's RYBREVANT is gradually gaining ground. Patients may develop resistance to TAGRISSO due to changes in the cancer cells, like increased MET proteins (called MET amplification) or new EGFR mutations that help the cancer grow despite treatment. Overcoming this resistance is important because it allows treatment to continue working and helps patients live longer. 

RYBREVANT from Johnson & Johnson has joined the broad first-line EGFR-mutated NSCLC market. The company also intends to launch the subcutaneous version of RYBREVANT. Given the prospects for Johnson & Johnson's EGFR x C-Met bispecific RYBREVANT in NSCLC, it is reasonable to assume that RYBREVANT has the potential to grow into a billion-dollar product.

The data show that chemotherapy plus RYBREVANT is an effective regimen, regardless of the baseline mechanism of resistance post-TAGRISSO, and therefore it remains a standard of care in this setting.