J&J’s RYBREVANT Shows Longest OS in EGFR Lung Cancer

Raritan, New Jersey, U.S., September 14, 2026

PAPILLON Trial Shows Long-Term Survival

The PAPILLON Phase III trial evaluated RYBREVANT in combination with platinum-based chemotherapy versus chemotherapy alone as a first-line treatment for patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. The study previously demonstrated a significant progression-free survival benefit for the RYBREVANT combination, establishing the regimen as an important targeted treatment approach for this difficult-to-treat form of lung cancer. In the latest overall survival analysis, patients receiving RYBREVANT plus chemotherapy achieved a median OS of 34.3 months, compared with 27.9 months in the chemotherapy arm. The unadjusted overall survival analysis produced a hazard ratio of 0.87 (95% CI, 0.66–1.14) with a P value of 0.307, meaning the primary intention-to-treat OS comparison did not demonstrate statistical significance. A major factor influencing interpretation was treatment crossover. Approximately 76% of eligible patients in the chemotherapy arm subsequently received RYBREVANT, potentially reducing the observable difference between the treatment groups in the intention-to-treat analysis. A prespecified crossover-adjusted analysis estimated a 43% reduction in the risk of death, with an OS hazard ratio of 0.57 and a nominal P value of 0.003. These adjusted findings provide additional context for interpreting the long-term survival data.

RYBREVANT Regimen Extends Disease Control

The overall survival findings complement previously demonstrated improvements in progression-free survival (PFS). RYBREVANT plus chemotherapy produced a median PFS2 of 28.3 months, compared with 17.5 months with chemotherapy alone, corresponding to a hazard ratio of 0.59 and a nominal P value below 0.0001. PFS2 measures the time from randomization until progression after the next line of treatment or death and can provide insight into whether the initial treatment strategy continues to influence disease control after subsequent therapy. The results therefore add to the evidence supporting RYBREVANT-based treatment in patients with EGFR exon 20 insertion-positive NSCLC. EGFR exon 20 insertion mutations are relatively uncommon genomic alterations that can drive tumor growth and have historically been associated with limited responses to conventional EGFR-targeted therapies. The development of mutation-directed treatments such as amivantamab represents an important advancement in precision oncology, allowing treatment strategies to be tailored to specific molecular drivers of disease.

Safety and Treatment Advances in EGFR NSCLC

RYBREVANT (amivantamab-vmjw) is a bispecific antibody designed to target EGFR and MET, two signaling pathways involved in tumor growth and survival. By binding to these targets, amivantamab is intended to interfere with oncogenic signaling and promote immune-mediated mechanisms against cancer cells. The PAPILLON findings build on the clinical development of RYBREVANT in EGFR-mutated NSCLC and demonstrate the importance of long-term follow-up in evaluating targeted cancer therapies. Johnson & Johnson is also developing newer formulations and treatment approaches intended to improve the administration experience associated with RYBREVANT-based therapy. The latest survival analysis is particularly relevant because patients with EGFR exon 20 insertion-positive advanced NSCLC have historically faced limited treatment options and poor outcomes. The 34.3-month median OS observed with RYBREVANT plus chemotherapy represents an important benchmark for the treatment landscape. However, the distinction between the unadjusted OS analysis and crossover-adjusted analysis remains important when reporting the findings. The primary intention-to-treat comparison was not statistically significant, while the prespecified crossover-adjusted analysis showed a significant reduction in the estimated risk of death. Accordingly, the results should be described accurately without characterizing the unadjusted analysis as a statistically significant OS improvement. Overall, the PAPILLON data reinforce the role of RYBREVANT plus chemotherapy as a targeted first-line treatment strategy for EGFR exon 20 insertion-positive advanced NSCLC and provide important long-term evidence for ongoing clinical and regulatory evaluation.

Source: Johnson & Johnson press release