Results from the Phase III PAPILLON study show that first-line amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) was associated with numerically longer overall survival compared with chemotherapy in patients with previously untreated advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (Ex20ins) mutations.

The findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

EGFR exon 20 insertions account for approximately 12% of EGFR-mutated NSCLC.

In PAPILLON (NCT04538664), 308 participants with previously untreated Ex20ins advanced NSCLC were randomised 1:1 to amivantamab-chemotherapy (n=153) or chemotherapy (n=155).

Participants in the chemotherapy arm were permitted to cross over to second-line amivantamab monotherapy after confirmed disease progression.

Overall survival was a key secondary endpoint.

At the March 20, 2026 data cutoff, with a median follow-up of 48.6 months, median overall survival was 34.3 months with amivantamab-chemotherapy versus 27.9 months with chemotherapy (HR 0.87; 95% CI, 0.66–1.14; P=0.307).

This represents a numerical improvement of 6.4 months in median overall survival.

Overall survival results generally favoured amivantamab-chemotherapy across predefined subgroups.

Among 128 participants in the chemotherapy arm who discontinued because of progressive disease, 97 (76%) received second-line amivantamab monotherapy.

After adjusting for on-protocol crossover using the prespecified inverse probability of censoring weighting (IPCW) model, amivantamab-chemotherapy demonstrated a significant survival benefit (IPCW HR 0.57; 95% CI, 0.39–0.82; nominal P=0.003).

The safety profile of intravenous amivantamab-chemotherapy was consistent with prior reports with intravenous amivantamab before subcutaneous amivantamab and prophylactic adverse event strategies were implemented.

Patient-reported outcomes also favoured amivantamab-chemotherapy, with prolonged time to worsening across several key symptom scales.

“PAPILLON demonstrated the longest reported median overall survival to date in EGFR exon 20 insertion-positive advanced NSCLC with first-line amivantamab-chemotherapy,” said Chul Kim, M.D., Division of Haematology and Oncology, Georgetown Cancer Institute, Washington, D.C.

“While crossover likely attenuated the hazard-ratio-based overall survival estimate, the adjusted analysis showed a substantially longer estimated survival benefit, supporting amivantamab-chemotherapy as a foundational first-line regimen for patients with Ex20ins advanced NSCLC.”

Source: International Association for the Study of Lung Cancer