Johnson and Johnson (J&J) has released new data from a Phase III trial showing that its combination treatment of Rybrevant (amivantamab) and Lazcluze (lazertinib) lowered the risk of death by 25% compared to AstraZeneca’s Tagrisso (osimertinib) in previously-untreated patients after 37.8 months of follow-up.
The results were presented at the European Lung Cancer Congress (ELCC 2025) taking place in Paris, France, from 26 to 29 March 2025. The company also noted that the median overall survival (OS) for the combination therapy, which has not yet been reached, is “projected to exceed beyond the median of three years observed for Tagrisso”.
J&J and AstraZeneca’s competition intensifies
Tagrisso, a tyrosine kinase inhibitor, has been the preferred treatment for EGFR-mutated non-small cell lung cancer (NSCLC) for the past few years. The therapy scored the approval in first-line setting from the US Food and Drug Administration (FDA) in 2018. Since then, Tagrisso has become one of the highest-grossing therapies in AstraZeneca’s portfolio, raking in $6.58 billion in sales in 2024.
J&J’s combination therapy of EGFRxMET bispecific antibody Rybrevant and an EGFR tyrosine kinase inhibitor Lazcluze scored the US FDA approval as a first-line treatment for NSCLC in patients with exon 19 deletions or exon 21 L858R substitutions, in August last year. That approval was based on progression-free survival (PFS) data from the Phase III MARIPOSA study.
Phase III MARIPOSA trial data
The head-to-head Phase III MARIPOSA study (NCT04487080) evaluated the combination treatment of Rybrevant and Lazcluze versus Tagrisso, and versus Lazcluze monotherapy as a first-line treatment in patients with locally advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations. The trial met its primary endpoint with a statistically significant and clinically meaningful improvement in PFS compared to Tagrisso.
“The survival curve demonstrates that Rybrevant and Lazcluze can help patients live longer compared to Tagrisso monotherapy, and suggests the benefit keeps growing over time,” said trial investigator Professor Nicolas Girard.
“We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR-mutated advanced non-small cell lung cancer.”
After three and a half years, 56% of the patients in the Rybrevant and Lazcluze combination group were alive, compared to 44% in the Tagrisso arm. Additionally, the J&J combination therapy prolonged the prolonged time to symptomatic progression (TTSP) by more than 14 months compared to Tagrisso.
The commonly observed adverse events (AEs) included skin infection (paronychia), infusion-related reactions, and rash. The most common grade 3 or higher AEs were skin reactions (rash, paronychia, and dermatitis acneiform) and elevated liver enzyme (alanine transaminase).
J&J is also developing a subcutaneous formulation for Rybrevant. In December 2024, the US FDA refused to approve the fixed combination of Rybrevant and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) in EGFR-mutated NSCLC patients. The regulatory agency cited manufacturing quality compliance issues and issued a complete response letter (CRL).
