Johnson & Johnson (J&J) has announced results from the final Overall Survival (OS) analysis of the phase 3 PAPILLON study evaluating first-line intravenous (IV) RYBREVANT (amivantamab) plus carboplatin-pemetrexed chemotherapy, versus chemotherapy alone, in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) exon 20 insertion (Ex20ins) mutations.

Patients treated with amivantamab plus chemotherapy achieved a median OS of 34.3 months. The median OS with chemotherapy alone was 27.9 months (Hazard Ratio [HR], 0.87; 95 percent Confidence Interval [CI], 0.66-1.14; p=0.307).

The combination of amivantamab plus chemotherapy showed a numerical difference in median OS by more than 6 months, despite 76 percent of eligible patients in the chemotherapy arm crossing over to second-line amivantamab after disease progression. This represents the longest reported median OS in this patient population, and is nearly twice the 16.2-month median OS reported in a real-world cohort of patients with EGFR exon 20 insertion-mutated NSCLC.

These results were presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

EGFR Ex20ins mutations account for approximately 12 percent of all EGFR mutations. Unlike more common EGFR mutations (exon 19 deletions and L858R), exon 20 insertion mutations have thus far been difficult to treat with targeted medicines; leaving patients with few treatment options, challenging side effects and poorer outcomes. Historically, median OS has ranged from approximately 16 to 24 months, with 5-year survival reported at just 8 percent.

Dr. Chul Kim, MD, MPH, Director of Thoracic Oncology, MedStar Georgetown University Hospital, said, “We’ve come a long way in treating EGFR exon 20 insertion-positive lung cancer, and these results demonstrate the lasting impact amivantamab 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.”

Amivantamab is a first-in-class bispecific antibody designed to dual-target EGFR and Mesenchymal-Epithelial Transition (MET), 2 key drivers of tumor growth and treatment resistance, while also engaging the immune system. It is currently approved for use in patients with EGFR-mutated advanced NSCLC across common (exon 19 deletions and exon 21 L858R substitution mutations) and exon 20 insertion mutations, in the first-line and second-line settings.

Yusri Elsayed, MD, MHSc, PhD, Global Therapeutic Area Head, Oncology, J&J, said, “We have long believed amivantamab could transform the outlook for patients with EGFR-mutated lung cancer by addressing key drivers of disease progression and treatment resistance. With the longest survival seen in this patient population, these results add to the growing body of evidence across common, atypical and exon 20 insertion EGFR mutations and further establish the regimen as a backbone therapy.”