RYBREVANT Plus Chemotherapy Delivers Longest Reported Survival in EGFR Exon 20 Insertion Lung Cancer
News related to:Johnson & Johnson · 3 min read
Johnson & Johnson's RYBREVANT® plus chemotherapy has delivered a significant breakthrough in the treatment of EGFR exon 20 insertion mutation-positive lung cancer, marking the longest reported median overall survival in this challenging patient population. The results, presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC), show that patients treated with the combination therapy achieved a median overall survival of 34.3 months, compared to 27.9 months for those receiving chemotherapy alone.
The Phase 3 PAPILLON study, which enrolled 308 patients, evaluated the efficacy and safety of RYBREVANT in combination with chemotherapy versus chemotherapy alone in newly diagnosed patients with advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR exon 20 insertion mutations. The primary endpoint of the study was progression-free survival (PFS), as assessed by blinded independent central review (BICR). Secondary endpoints included overall response rate (ORR), PFS after first subsequent therapy, time to symptomatic progression, and overall survival.
According to the data, RYBREVANT plus chemotherapy demonstrated a significant overall survival benefit, reducing the risk of death by 43 percent. This benefit was further highlighted by a 10-month extension in progression-free survival through second disease progression (PFS2) compared to chemotherapy alone. At the clinical cutoff, 12 percent of patients remained on first-line treatment, compared to none in the chemotherapy arm.
Dr. Chul Kim, Director of Thoracic Oncology at MedStar Georgetown University Hospital, commented, "These results demonstrate the lasting impact RYBREVANT plus chemotherapy can have in helping patients live longer. Patients are continuing treatment years after they started, which speaks to the durability of this approach and its value as a first-line treatment for this disease."
Dr.
The safety profile of RYBREVANT plus chemotherapy was consistent with previous reports, with no new safety signals observed. The most common treatment-related adverse events included paronychia, neutropenia, and rash, occurring in at least 30 percent of patients.
Historically, patients with EGFR exon 20 insertion mutations have faced poor outcomes, with a median overall survival ranging from approximately 16 to 24 months and a five-year survival rate of just 8 percent. The new findings from the PAPILLON study reset survival expectations for this historically difficult-to-treat lung cancer population.
The results build on the primary PAPILLON analysis, which demonstrated a 60 percent improvement in progression-free survival with first-line RYBREVANT plus chemotherapy versus chemotherapy alone. These findings support global approvals of the regimen in this setting and were simultaneously published in The New England Journal of Medicine.
RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) received U.S. FDA approval in December 2025 and is approved in multiple markets worldwide for the treatment of adults with EGFR-mutated non-small cell lung cancer (NSCLC), including those with exon 19 deletions, exon 21 L858R substitution mutations, and exon 20 insertion mutations. It is the only subcutaneous therapy approved for these EGFR-mutated NSCLC populations and may be used as monotherapy or in combination with LAZCLUZE® (lazertinib) or chemotherapy, depending on the specific mutation and treatment setting.
The effectiveness of RYBREVANT FASPRO is supported by the established clinical profile of RYBREVANT, including data from multiple Phase 3 studies such as MARIPOSA, which demonstrated improvements in progression-free and overall survival when used in combination with LAZCLUZE in first-line advanced EGFR-mutated NSCLC.
These results underscore the importance of targeted therapies in the treatment of EGFR-mutated NSCLC and highlight the potential of RYBREVANT in transforming the outlook for patients with EGFR exon 20 insertion mutations.