Johnson & Johnson’s bispecific antibody RYBREVANT, when added to first‑line chemotherapy, produced the longest reported median overall survival (OS) to date in patients with EGFR exon 20 insertion‑positive non‑small cell lung cancer (NSCLC), according to the final analysis of the phase III PAPILLON trial.
In the trial, patients receiving RYBREVANT plus chemotherapy lived a median of 34.3 months versus 27.9 months for chemotherapy alone (HR 0.87; 95 % CI 0.66‑1.14; nominal P = 0.307). After adjusting for the crossover of 76 % of chemotherapy‑only patients to RYBREVANT at progression, the risk of death was reduced by 43 % (HR 0.57; 95 % CI 0.39‑0.82; nominal P = 0.003). The combination also extended PFS2 by more than ten months (28.3 months vs 17.5 months; HR 0.59; P < 0.0001) and allowed 12 % of patients to remain on first‑line therapy at the analysis cutoff, compared with none on chemotherapy alone. Patients reported a delayed worsening of key lung‑cancer symptoms.
Durable Benefit and Differentiated Mechanism
RYBREVANT is a first‑in‑class bispecific antibody that simultaneously targets EGFR and MET, two pathways that drive tumor growth and resistance. The agent is already approved for multiple EGFR‑mutated NSCLC settings, including exon 20 insertions.
Dr. Chul Kim of MedStar Georgetown University Hospital noted that these data establish RYBREVANT as a new standard of care in the first‑line setting for a patient population with historically limited options.
Overall Survival, Progression‑Free Survival and Safety Highlights
- Median OS: 34.3 months (RYBREVANT + chemo) vs 27.9 months (chemo alone). Adjusted OS: 43 % lower risk of death (HR 0.57; P = 0.003).
- PFS2: 28.3 months vs 17.5 months (HR 0.59; P < 0.0001).
- Treatment durability: 12 % of patients on the combination remained on first‑line therapy; 0 % on chemo alone.
- Patient‑reported outcomes: slower deterioration of respiratory symptoms versus chemo alone.
The safety profile of the combination was consistent with prior studies, with no new signals. Common treatment‑related adverse events (≥30 %): paronychia, neutropenia and rash.
About the PAPILLON Trial
PAPILLON (randomized, open‑label, phase III) enrolled 308 patients with advanced or metastatic EGFR exon 20 insertion NSCLC. The primary endpoint was progression‑free survival per RECIST v1.1 (BICR). Key secondary endpoints included overall survival, overall response rate, time to symptomatic progression and PFS after the first subsequent therapy. Patients receiving chemotherapy alone could cross over to RYBREVANT upon progression.
Johnson & Johnson continues to advance its oncology pipeline, positioning RYBREVANT as a cornerstone therapy for EGFR‑mutated NSCLC.
