PAPILLON Phase 3 Trial Redefined Treatment Standards

The PAPILLON trial, conducted by Janssen Research & Development of Johnson & Johnson (JNJ), was a randomized, open-label, global Phase 3 trial enrolling 308 patients with treatment-naïve EGFR exon20 insertion-mutant advanced or metastatic non-small cell lung cancer (NSCLC). Libtayo (amivantamab-vmjw), a bispecific antibody targeting both the epithelial growth factor receptor (EGFR) and the mesenchymal-epithelial transition factor (MET), was combined with carboplatin and pemetrexed. The control group received carboplatin and pemetrexed, the standard of care at the time. The trial has completed enrollment and is currently in long-term follow-up.

Reduced Risk of Disease Progression by 60%

Median progression-free survival (PFS) based on independent central review was 11.4 months in the combination group versus 6.7 months in the chemotherapy group, with a hazard ratio (HR) of 0.40, 95% confidence interval (CI) 0.30–0.53, and a p-value <0.0001. Objective response rate (ORR) was also superior at 73% versus 47%, and median duration of response was 9.7 months versus 4.4 months in the combination group. At 18 months, the PFS rate was 31% versus 3%, demonstrating not only improved response rates but also sustained disease control. Adverse events such as rash, nail toxicity, stomatitis, infusion-related reactions, and edema are operational and cost-related factors requiring management in real-world prescribing.

U.S., EU, and Japan Approvals Confirm Commercialization

On March 1, 2024, the FDA approved Libtayo in combination with carboplatin and pemetrexed as a first-line treatment for locally advanced or metastatic NSCLC with EGFR exon20 insertion mutations. The agency also converted the accelerated approval for Libtayo as a monotherapy following platinum-based chemotherapy to full approval. This decision was made without a vote from the Oncologic Drugs Advisory Committee (ODAC). On June 28, 2024, the European Commission approved the same first-line combination indication, and the European Medicines Agency (EMA) converted its conditional marketing authorization to a standard marketing authorization on June 27, 2024. In Japan, Libtayo was approved on September 24, 2024, following review by the Pharmaceuticals and Medical Devices Agency (PMDA), with PAPILLON's PFS superiority serving as a key basis.

Competition Shifts to Later-line Therapies and Dosing Convenience

Chemotherapy is no longer the independent first-line standard in the U.S. and EU, and the direct competitive drug is the oral EGFR inhibitor Zegfrovy (sunvozertinib) from Dizal Pharmaceuticals. The FDA granted accelerated approval to Zegfrovy on July 2, 2025, for use after platinum-based chemotherapy, with an ORR of 46% and a median duration of response of 11.1 months in the WU-KONG1B trial. Takeda Pharmaceutical (TAK)'s Exkivity (mobocertinib) was withdrawn from the U.S. label following failure in a confirmatory Phase 3 trial and has exited the first-line treatment competition. The global EGFR exon20 insertion-mutant TKI market is projected to reach USD 126.9 million by 2027, while the overall EGFR NSCLC market is estimated at USD 7.5 billion in 2024. JNJ's combined sales of Libtayo and Razyreld (amivantamab-vmjw) reached USD 734 million in 2025, up from USD 327 million in 2024.