Johnson & Johnson RYBREVANT Amivantamab NSCLC Regimen Delivers Longest Reported Survival in EGFR Exon 20 Lung Cancer

Johnson & Johnson’s RYBREVANT Amivantamab NSCLC combination has posted the longest reported median overall survival to date in EGFR exon 20 insertion mutation-positive non-small cell lung cancer, according to final results from the Phase 3 PAPILLON study. Patients treated with RYBREVANT (amivantamab-vmjw) plus carboplatin-pemetrexed chemotherapy achieved a median overall survival of 34.3 months, compared with 27.9 months for chemotherapy alone, the company announced on September 13, 2026.

The data were presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea, as Late-Breaking Abstract #PL.03.03. The combination extended median overall survival by more than six months despite 76 percent of eligible patients in the chemotherapy-alone arm crossing over to second-line RYBREVANT after disease progression. A prespecified analysis that accounted for this crossover showed the RYBREVANT based regimen reduced the risk of death by 43 percent (hazard ratio 0.57; 95 percent confidence interval, 0.39–0.82; nominal P=0.003).

RYBREVANT Amivantamab NSCLC Data Show 34.3-Month Median Overall Survival in PAPILLON

The unadjusted final analysis showed a hazard ratio of 0.87 (95 percent confidence interval, 0.66-1.14; P=0.307) for RYBREVANT plus chemotherapy versus chemotherapy alone. Long-term follow-up also showed the combination extended progression-free survival through second disease progression (PFS2) by more than ten months versus chemotherapy alone, 28.3 months compared with 17.5 months (hazard ratio 0.59; 95 percent confidence interval, 0.45-0.77; nominal P<0.0001).Twelve percent of patients remained on first-line treatment at the clinical cutoff, compared with no patients in the chemotherapy-alone arm, and patient-reported outcomes favored the combination by delaying the worsening of several key lung cancer symptoms.

These findings build on the primary PAPILLON analysis, which showed a statistically significant 60 percent improvement in progression-free survival, the study’s primary endpoint, and was consistent across subgroups including patients with brain metastases, EGFR exon 20 insertion variants, and TP53 co-mutations. That earlier analysis, which supported global regulatory approvals of the regimen, was published in The New England Journal of Medicine.

Learn More

AstraZeneca Enhertu DESTINY-Lung04 Trial Demonstrates 14.3-Month Median PFS in First-Line HER2-Mutant NSCLC

Why RYBREVANT Amivantamab NSCLC Results Matter for EGFR Exon 20 Insertion Patients

EGFR exon 20 insertion mutations account for approximately 12 percent of all EGFR mutations and, unlike the more common exon 19 deletion and L858R alterations, have historically been difficult to treat with targeted medicines. Median overall survival for this population has ranged from roughly 16 to 24 months, with a five-year survival rate of just 8 percent, according to the real-world data cited in the release. The new RYBREVANT Amivantamab NSCLC survival figures are nearly double that historical median, a milestone researchers say resets expectations for a population that has faced limited options and challenging side effects.

RYBREVANT is a first-in-class, fully human bispecific antibody engineered to dual-target EGFR and the mesenchymal-epithelial transition (MET) receptor, two drivers of tumor growth and treatment resistance, while also engaging the immune system. It is approved for EGFR-mutated advanced NSCLC across common mutations (exon 19 deletions and exon 21 L858R substitutions) and exon 20 insertion mutations, in both first- and second-line settings.

“We’ve come a long way in treating EGFR exon 20 insertion-positive lung cancer, and these results demonstrate the lasting impact RYBREVANT plus chemotherapy can have in helping patients live longer,” said Dr. Chul Kim, M.D., M.P.H., Director of Thoracic Oncology at MedStar Georgetown University Hospital. “Patients are continuing treatment years after they started, which speaks to the durability of this approach.”

“We have long believed RYBREVANT could transform the outlook for patients with EGFR-mutated lung cancer,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson, adding that the data further establish the regimen as a backbone therapy across mutation subtypes.

Learn More

Novo Nordisk Ziltivekimab ZEUS Trial: Phase 3 Cardiovascular Readout Misses Primary MACE Reduction Target

RYBREVANT Amivantamab NSCLC Safety Profile and Additional WCLC 2026 Data

The safety profile of IV RYBREVANT plus chemotherapy in the final PAPILLON analysis was consistent with previous reports from studies conducted before prophylactic strategies were introduced, and no new safety signals emerged with longer follow-up. Treatment-related adverse events occurring in at least 30 percent of patients included paronychia (60 percent), neutropenia (60 percent) and rash (58 percent).

Additional RYBREVANT Amivantamab NSCLC research presented at WCLC 2026 highlighted continued efforts to improve the treatment experience. The COPERNICUS study (Abstract #MO12.09) is evaluating prophylactic strategies designed to reduce key treatment-related events, while the PALOMA-2 study (Abstract #PT2.03.06) is assessing subcutaneous administration. Johnson & Johnson also markets RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj), a subcutaneous formulation co-formulated with Halozyme’s ENHANZE drug-delivery technology that received U.S. FDA approval in December 2025 and offers once-monthly dosing for eligible patients following an initial weekly schedule.

What’s Next for RYBREVANT Amivantamab NSCLC Treatment Following the PAPILLON Final Analysis

PAPILLON (NCT04538664) enrolled 308 patients in a randomized, open-label Phase 3 study comparing first-line RYBREVANT plus chemotherapy against chemotherapy alone in newly diagnosed patients with advanced or metastatic NSCLC bearing EGFR exon 20 insertion mutations. The primary endpoint was progression-free survival by blinded independent central review using RECIST v1.1 criteria, with secondary endpoints including overall response rate, PFS after first subsequent therapy, time to symptomatic progression and overall survival. Patients assigned to chemotherapy alone were permitted to cross over to second-line RYBREVANT monotherapy after BICR-confirmed disease progression.

Non-small cell lung cancer accounts for 80 to 85 percent of all lung cancer cases worldwide, and EGFR mutations are present in 10 to 15 percent of Western NSCLC adenocarcinoma patients and 40 to 50 percent of Asian patients. Exon 20 insertion mutations are the third-most prevalent activating EGFR alteration, with a real-world five-year overall survival of 8 percent in the frontline setting, compared with 19 percent for patients with the more common exon 19 deletion or L858R mutations. Current National Comprehensive Cancer Network guidelines list amivantamab-based regimens, including in combination with LAZCLUZE (lazertinib), among preferred options for EGFR-mutated NSCLC, including in patients with brain metastases. RYBREVANT-based therapies are also being investigated in other solid tumors, including head and neck and colorectal cancers, extending the potential reach of the RYBREVANT Amivantamab NSCLC platform beyond lung cancer.

The table below summarizes the core RYBREVANT Amivantamab NSCLC efficacy findings from the PAPILLON final analysis.

RYBREVANT Amivantamab NSCLC PAPILLON Final Overall Survival Analysis

Treatment-Related Adverse Events (≥30% of Patients)

PAPILLON Study Design Summary

The disease burden data below provide context for why the RYBREVANT Amivantamab NSCLC survival results are considered clinically significant.

EGFR Exon 20 Insertion NSCLC: Disease Burden Context