Final results from the landmark PAPILLON trial, which changed the standard of care for a difficult-to-treat rare form of lung cancer, confirm that amivantamab, when added to chemotherapy, provides durable clinical benefit and the longest median overall survival reported to date for people with the disease.
The study, conducted at Georgetown University's Lombardi Comprehensive Cancer Center and 231 other international sites, previously demonstrated a major progression-free survival benefit in non-small cell lung cancer (NSCLC) with an uncommon mutation (a EGFR exon 20 insertion mutation) leading to FDA approval of amivantamab (RybrevantⓇ) in March 2024.
The final overall survival analysis results from the phase III trial were presented by Georgetown Lombardi's Chul Kim, MD, MPH , as part of a Presidential plenary at the 2026 World Conference on Lung Cance r in Seoul, South Korea, on September 14.
"These new findings are meaningful because they represent what we believe is the longest median overall survival reported for people with this form of lung cancer. Historically, median overall survival in this patient population was about 1.5 to 2 years. In this trial, it reached 34.3 months—nearly 3 years," says Kim, associate professor of medicine at Georgetown University School of Medicine and director of thoracic oncology at MedStar Georgetown University Hospital . "The final overall survival analysis did not reach statistical significance, but the study had limited statistical power for this endpoint, which was further reduced by the substantial crossover between treatment groups. About three-quarters of eligible patients initially assigned to chemotherapy subsequently received amivantamab after their cancer progressed.
"When we account for that crossover, the overall survival benefit becomes much more pronounced," Kim says. "Taken together with the clear progression-free survival benefit, these findings further support amivantamab plus chemotherapy as a foundational first-line treatment for these patients."
Approximately 1% to 2% of all advanced NSCLCs carry an EGFR exon 20 insertion mutation, representing about 1,500–2,500 annual diagnoses in the U.S. These patients also account for 5-10% of all EGFR-mutated NSCLC cases.
Some of the final key final findings from PAPILLON include:
● Overall Survival (OS): Amivantamab plus chemotherapy versus chemotherapy alone extended overall survival by a clinically meaningful 6 months (34.3 vs 27.9 months).
● Progression-Free Survival (PFS), meaning no significant cancer growth or death occurred, reached 11.4 months with amivantamab plus chemotherapy versus 6.7 months with chemotherapy alone, cutting disease progression risk by 60%.
● Response Rates: Objective response rates, which show the percentage of patients whose cancer shrinks or disappears after treatment, were 73% in the amivantamab arm compared to 40% in the control chemotherapy arm.
● Patient-reported quality-of-life outcomes favored the amivantamab arm.
Amivantamab is part of a new class of drugs called bispecific antibodies, a targeted therapy designed to bind to two different targets.
The trial also underscores the importance of next-generation sequencing, Kim noted. This genomic testing allows physicians to identify rare alterations such as EGFR exon 20 insertions and match patients with therapies specifically designed for their tumors. Next-generation sequencing is routinely used at Georgetown Lombardi and other comprehensive cancer centers.
Researchers are now looking at amivantamab-based strategies in atypical EGFR-mutant NSCLC and other tumor types, including head and neck and colorectal cancers.
