RYBREVANT® plus chemotherapy shows survival benefit in treated EGFR-mutated lung cancer

Johnson & Johnson recently shared updated findings from the Phase 3 MARIPOSA-2 study at the European Society of Medical Oncology (ESMO) 2024 Congress, highlighting the efficacy of RYBREVANT® (amivantamab-vmjw) combined with chemotherapy for treating advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations. The study demonstrated significant benefits in post-progression outcomes and showed a trend of improved overall survival (OS) for patients receiving the combined treatment compared to those on chemotherapy alone.

Key results from the study showed that, at a median follow-up of 18.1 months, 50% of patients treated with RYBREVANT® plus chemotherapy were alive at the 18-month mark, compared to 40% of patients on chemotherapy alone. The median overall survival was 17.7 months for the combined treatment versus 15.3 months for chemotherapy alone, with a hazard ratio (HR) of 0.73.

The study also found that the rate of treatment discontinuation was significantly lower for the RYBREVANT® plus chemotherapy group, with 22% of patients remaining on therapy at 18 months compared to just 4% in the chemotherapy-only group. The median time to treatment discontinuation was 10.4 months for the combined treatment versus 4.5 months for chemotherapy, with a hazard ratio of 0.42.

Additionally, the risk of symptomatic progression was reduced by 27% in patients treated with the combined therapy, and the median time to symptomatic progression was 16.0 months compared to 11.8 months for those on chemotherapy alone. The time to subsequent therapy was also longer for the RYBREVANT® combination (median of 12.2 months) compared to chemotherapy (6.6 months), with a hazard ratio of 0.51. Furthermore, the risk of second disease progression or death was reduced by 36% with the combined treatment, with median progression-free survival after first subsequent therapy (PFS2) being 16.0 months versus 11.6 months for chemotherapy alone.

The safety profile of RYBREVANT® combined with chemotherapy was consistent with the known profiles of the individual treatments, with 11% of patients discontinuing RYBREVANT® due to adverse reactions.

Joshua Bauml, M.D., Vice President at Johnson & Johnson, mentioned that the findings underscore the potential of this combination therapy to provide significant benefits to patients with limited treatment options. The combination of RYBREVANT® and chemotherapy has already received approval from the European Commission in August 2024 for treating patients with previously treated NSCLC with common EGFR mutations, based on the study's demonstrated efficacy and safety.

The MARIPOSA-2 study is a Phase 3 trial that randomized patients with locally advanced or metastatic EGFR-mutated NSCLC, who had progressed on or after osimertinib, to receive either RYBREVANT® plus chemotherapy, RYBREVANT® plus chemotherapy with LAZCLUZE™, or chemotherapy alone. The primary endpoints were progression-free survival (PFS) compared to chemotherapy as assessed by blinded independent central review. Secondary endpoints included overall survival, objective response, duration of response, and time to subsequent therapy, among others. The study involved 657 patients in total.

RYBREVANT® is a fully-human bispecific antibody targeting EGFR and MET, approved for treating NSCLC with EGFR exon 20 insertion mutations. It is available in the U.S., Europe, and other markets. In combination with LAZCLUZE™, it is also approved for first-line treatment of NSCLC with EGFR exon 19 deletions or L858R substitution mutations in the U.S.

Various clinical trials are ongoing to further evaluate RYBREVANT® in different combinations and settings, including other advanced and metastatic cancers. These trials aim to expand the therapeutic applications of RYBREVANT® and improve outcomes for patients with challenging cancer types.