Johnson & Johnson has reported final overall survival results from the Phase III PAPILLON study evaluating first-line intravenous RYBREVANT, or amivantamab-vmjw, plus carboplatin-pemetrexed chemotherapy in patients with advanced non-small cell lung cancer carrying EGFR exon 20 insertion mutations.
Patients treated with the combination achieved a median overall survival of 34.3 months, compared with 27.9 months for chemotherapy alone.
The combination extended median overall survival by more than six months despite 76% of eligible patients in the chemotherapy arm crossing over to second-line RYBREVANT following disease progression.
Johnson & Johnson said the result represents the longest reported median overall survival in this patient population and is nearly twice the historical median.
The findings were presented during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer.
EGFR exon 20 insertion mutations account for approximately 12% of all EGFR mutations and have historically been difficult to treat with targeted therapies.
Median overall survival in this population has historically ranged from approximately 16 to 24 months, with five-year survival reported at around 8%.
RYBREVANT is a first-in-class bispecific antibody designed to target both EGFR and MET, two drivers of tumour growth and treatment resistance, while also engaging the immune system.
It is currently approved in EGFR-mutated advanced NSCLC across common EGFR mutations and exon 20 insertion mutations in first- and second-line settings.
“We've come a long way in treating EGFR exon 20 insertion-positive lung cancer, and these results demonstrate the lasting impact RYBREVANT plus chemotherapy can have in helping patients live longer,” said Dr Chul Kim, Director of Thoracic Oncology at MedStar Georgetown University Hospital.
“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.”
In the protocol-specified final analysis, the hazard ratio for overall survival was 0.87, with a 95% confidence interval of 0.66 to 1.14.
A prespecified analysis accounting for crossover to RYBREVANT in the chemotherapy arm showed a 43% reduction in the risk of death, with a hazard ratio of 0.57.
Long-term follow-up also showed that RYBREVANT plus chemotherapy extended progression-free survival through second disease progression by more than 10 months, reaching 28.3 months compared with 17.5 months for chemotherapy alone.
Twelve per cent of patients remained on first-line treatment at the clinical cut-off, compared with no patients in the chemotherapy arm.
Patient-reported outcomes also favoured the combination, with delayed worsening of several key lung cancer symptoms.
The safety profile of intravenous RYBREVANT plus chemotherapy was consistent with previous reports, with no new safety signals observed during longer follow-up.
The most common treatment-related adverse events occurring in at least 30% of patients included paronychia at 60%, neutropenia at 60% and rash at 58%.
The results build on the primary PAPILLON analysis, which showed a statistically significant 60% improvement in progression-free survival with first-line RYBREVANT plus chemotherapy compared with chemotherapy alone.
Johnson & Johnson is also evaluating approaches to improve the treatment experience, including prophylactic strategies in the COPERNICUS study and subcutaneous administration through RYBREVANT FASPRO in the PALOMA-2 study.
