Johnson & Johnson’s RYBREVANT and LAZCLUZE show unprecedented survival advantage in lung cancer trial

Johnson & Johnson has revealed transformative results from the Phase 3 MARIPOSA clinical trial, positioning the combination of RYBREVANT (amivantamab-vmjw) and LAZCLUZE (lazertinib) as a groundbreaking therapy for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The findings establish the combination as the first and only treatment to deliver a statistically significant improvement in overall survival (OS) compared to the existing standard of care, osimertinib, in first-line therapy.

What Makes the MARIPOSA Trial Results Significant?

Lung cancer remains the leading cause of cancer-related deaths globally, with NSCLC accounting for up to 85% of cases. For patients with EGFR-mutated NSCLC, treatment advancements are critical, as fewer than 20% survive beyond five years. Johnson & Johnson’s announcement of the MARIPOSA trial results marks a turning point in addressing this unmet need.

The study demonstrated that the RYBREVANT-LAZCLUZE combination not only surpasses osimertinib in terms of progression-free survival (PFS) but also extends median overall survival by more than one year. OS, widely regarded as the gold standard in cancer treatment, directly measures the ability of a therapy to prolong life—a key concern for patients and clinicians alike.

According to Dr Stephen Liu of Georgetown University, who led aspects of the MARIPOSA trial, this combination provides a clearer picture of how treatment impacts the entire disease trajectory. Unlike PFS, OS encapsulates the comprehensive benefit of first-line therapies in a way that resonates more deeply with patients.

Understanding the Science Behind the Combination Therapy

RYBREVANT, a fully human bispecific antibody, targets two critical pathways in cancer growth: EGFR and MET. Combined with LAZCLUZE, a third-generation tyrosine kinase inhibitor (TKI) that penetrates the brain and spares healthy EGFR cells, the regimen attacks EGFR-mutated cancer from multiple fronts. This dual-action approach addresses not only systemic cancer progression but also intracranial metastases, a frequent complication in NSCLC.

The MARIPOSA trial enrolled 1,074 patients with locally advanced or metastatic NSCLC harbouring EGFR exon 19 deletions or L858R substitution mutations. Participants were randomly assigned to receive either the RYBREVANT-LAZCLUZE regimen or osimertinib. Primary endpoints included PFS, while secondary outcomes focused on OS, objective response rates, and intracranial progression-free survival.

The trial also reported a manageable safety profile for the combination therapy. Although venous thromboembolic events were observed, Johnson & Johnson noted that administering oral anticoagulants during the first four months significantly reduced these risks, reinforcing the regimen’s viability as a first-line option.

Expert Insights: A Game-Changer for EGFR-Positive Patients

Dr Yusri Elsayed, Johnson & Johnson’s Global Therapeutic Area Head for Oncology, emphasised the significance of these results, calling them “transformative” for patients worldwide. With limited treatment options and dismal survival rates for advanced EGFR-mutated NSCLC, extending median OS by more than a year represents a major step forward.

Marcia Horn, President of the International Cancer Advocacy Network, highlighted the importance of these findings for patients and their families. She noted that every clinical breakthrough brings renewed hope in the fight against this devastating disease.

Regulatory Approvals and Future Implications

The MARIPOSA trial builds on the established approvals of RYBREVANT and LAZCLUZE. Currently, the combination is authorised in the U.S. and Europe for the first-line treatment of EGFR-mutated NSCLC. Johnson & Johnson plans to present the full data at an upcoming major medical conference and share the findings with global regulatory authorities to expand treatment access.

These developments pave the way for further exploration of chemotherapy-free regimens that improve both survival rates and quality of life for NSCLC patients. With RYBREVANT-LAZCLUZE setting a new benchmark, the oncology community is optimistic about the potential for continued advancements in targeted lung cancer therapies.

Global Impact of EGFR-Mutated NSCLC

EGFR mutations, particularly exon 19 deletions and L858R substitutions, drive a significant proportion of NSCLC cases, affecting up to 50% of Asian patients and 10-15% of Western populations. Despite advancements in TKIs, the five-year survival rate remains below 20%. The MARIPOSA trial results offer new hope for patients facing these grim statistics, heralding a future where personalised medicine can reshape outcomes.

A New Standard of Care Emerges

The combination of RYBREVANT and LAZCLUZE is not just a treatment; it represents a paradigm shift in the management of EGFR-mutated NSCLC. By delivering unprecedented survival benefits, the regimen redefines the expectations for first-line therapies and provides patients with a much-needed lifeline in their fight against lung cancer.