PAPILLON Final Analysis: Amivantamab Plus Chemotherapy Delivers 34.3-Month Median OS in EGFR Exon 20 Insertion NSCLC
核心洞察
Final Phase 3 PAPILLON analysis showed first-line amivantamab plus chemotherapy achieved a median overall survival of 34.3 months in EGFR (搜索) exon 20 insertion-positive advanced NSCLC.
Chemotherapy alone produced a median OS of 27.9 months, with the protocol-specified hazard ratio of 0.87 not reaching statistical significance.
A prespecified crossover-adjusted analysis, accounting for 76% of control patients who crossed over to amivantamab, showed a 43% reduction in risk of death.
First-line treatment with amivantamab plus chemotherapy produced a median overall survival (OS) of 34.3 months in the protocol-specified final analysis of the Phase 3 PAPILLON study, according to results presented at the IASLC 2026 World Conference on Lung Cancer Presidential Symposium. The figure represents the longest reported median OS in EGFR (搜索) exon 20 insertion mutation-positive non-small cell lung cancer (搜索) (NSCLC), a subtype that has historically carried a real-world five-year OS of just eight percent in the frontline setting.
The randomized, open-label Phase 3 PAPILLON study (NCT04538664) enrolled 308 patients with newly diagnosed advanced or metastatic NSCLC characterized by EGFR (搜索) exon 20 insertion mutations. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review using RECIST v1.1 guidelines.
Overall Survival Results and Crossover Adjustment
In the final analysis, amivantamab plus chemotherapy demonstrated a median OS of 34.3 months versus 27.9 months for chemotherapy alone (HR, 0.87; 95% CI, 0.66-1.14; p=0.307). The protocol-specified analysis did not meet statistical significance, a result that investigators attribute in part to the high rate of treatment crossover: 76 percent of eligible patients in the chemotherapy arm crossed over to second-line amivantamab after disease progression.
A prespecified analysis adjusting for treatment crossover showed a significant overall reduction in the risk of death by 43 percent (HR, 0.57; 95% CI, 0.39-0.82; nominal p=0.003). Twelve percent of patients in the combination arm remained on first-line treatment at the clinical cut-off date, compared with no patients in the chemotherapy arm.
"We've come a long way in treating EGFR (搜索) exon 20 insertion-positive lung cancer, and these results demonstrate the lasting impact amivantamab plus chemotherapy can have in helping patients live longer," said Dr. Chul Kim, M.D., M.P.H., Director of Thoracic Oncology, 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."
Durability Beyond First Progression
Long-term follow-up provided further evidence of durable benefit, with amivantamab plus chemotherapy extending progression-free survival through second disease progression (PFS2) by more than 10 months compared with chemotherapy alone (28.3 vs. 17.5 months; HR, 0.59; 95% CI, 0.45-0.77; nominal p<0.0001). Patient-reported outcomes also favored the combination, delaying the worsening of several key lung cancer symptoms compared with chemotherapy alone.
"We have long believed amivantamab could transform the outlook for patients with EGFR (搜索)-mutated lung cancer by addressing key drivers of disease progression and treatment resistance," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "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."
Safety Profile
The safety profile of intravenous amivantamab plus chemotherapy was consistent with previous reports from studies conducted before prophylactic strategies were introduced, with no new safety signals observed with longer follow-up. The most common treatment-related adverse events occurring in at least 30 percent of patients included paronychia (60 percent), neutropenia (60 percent) and rash (58 percent).
Building on the Primary PAPILLON Analysis
The overall survival findings build on the primary PAPILLON analysis, which demonstrated a statistically significant and clinically meaningful 60 percent improvement in PFS (the primary endpoint) with first-line amivantamab plus chemotherapy versus chemotherapy alone. Clinical benefit in the primary analysis was consistent across key patient subgroups, including patients with brain metastases (搜索), EGFR (搜索) exon 20 insertion variants and TP53 (搜索) co-mutations. Those results, which supported global approvals of the regimen in this setting, were simultaneously published in The New England Journal of Medicine.
"For patients with EGFR (搜索) exon 20 insertion-mutated non-small cell lung cancer (搜索), the treatment chosen at the outset can make a profound difference," said Henar Hevia, Ph.D., EMEA Therapeutic Area Head, Oncology, Johnson & Johnson. "These long-term PAPILLON results demonstrate the longest reported median overall survival to date in this disease, highlighting the importance of early identification and ensuring patients can access the most effective treatment approach from the beginning. This represents meaningful progress for a patient population that has historically faced poor outcomes and limited targeted treatment options."
Amivantamab Mechanism and Approved Indications
Amivantamab is a fully-human EGFR (搜索)-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system. The European Commission has approved amivantamab, both intravenous and subcutaneous, in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, among other indications. Subcutaneous amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE drug delivery technology.
Additional data presented at WCLC 2026 highlight ongoing research across intravenous and subcutaneous amivantamab, including prophylactic strategies evaluated in the COPERNICUS study (Abstract #MO12.09) and subcutaneous administration evaluated in the PALOMA-2 study (Abstract #PT2.03.06).
Disease Burden and Unmet Need
In Europe, an estimated 484,306 people were diagnosed with lung cancer in 2022, with NSCLC accounting for 85 percent of all lung cancer cases. EGFR (搜索) mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients. EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.
Patients with EGFR (搜索) exon 20 insertion mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR exon 19 deletion or exon 21 L858R mutations, who have a real-world five-year OS of 19 percent. The five-year survival rate for all patients with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors is less than 20 percent, and between 25 and 32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment.