- RYBREVANT plus chemotherapy demonstrates durable benefit with a differentiated approach that dual-targets EGFR and MET

- Results mark significant progress for a patient population with poor outcomes and a historical five-year survival rate of just 8%

SEOUL, South Korea, Sept. 13, 2026 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced results from the final overall survival (OS) analysis of the Phase 3 PAPILLON study evaluating first-line intravenous (IV) RYBREVANT (amivantamab-vmjw) plus carboplatin-pemetrexed chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) mutations. Patients treated with the combination achieved a median OS of nearly three years (34.3 months), compared with 27.9 months for chemotherapy alone. The combination extended median OS by more than six months, despite 76 percent of eligible patients in the chemotherapy arm crossing over to second-line RYBREVANT after disease progression. This represents the longest reported median OS in this patient population, which is nearly twice the historical median.1

These results were presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) (Late-breaking Abstract #PL.03.03).

Resetting survival expectations for patients with historically poor outcomes

EGFR exon 20 insertion mutations account for approximately 12 percent of all EGFR mutations.2 Unlike more common EGFR mutations (exon 19 deletions and L858R), exon 20 insertion mutations have been difficult to treat with targeted medicines, leaving patients with few treatment options, challenging side effects and poorer outcomes.3 Historically, median overall survival has ranged from approximately 16 to 24 months, with five-year survival reported at just eight percent.4,5,6

RYBREVANT is a first-in-class bispecific antibody designed to dual-target EGFR and mesenchymal-epithelial transition (MET), two key drivers of tumor growth and treatment resistance, while also engaging the immune system.7,8,9,10 It is currently approved for use in patients with EGFR-mutated advanced NSCLC across common (exon 19 deletions and exon 21 L858R substitution mutations) and exon 20 insertion mutations, in the first- and second-line settings.11

Expert and company perspectives on longer survival in historically difficult-to-treat lung cancer

"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, MedStar Georgetown University Hospital. "Patients are continuing treatment years after they started, which speaks to the durability of this approach and its value as a first-line treatment for this disease."

"We have long believed RYBREVANT could transform the outlook for patients with EGFR-mutated lung cancer by addressing key drivers of disease progression and treatment resistance," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "With the longest survival seen in this patient population, these results add to the growing body of evidence across common, atypical and exon 20 insertion EGFR mutations and further establish the regimen as a backbone therapy."

Detailed overall survival results

In the protocol-specified final analysis, RYBREVANT plus chemotherapy demonstrated a median OS of nearly three years (34.3 months) compared to approximately two years (27.9 months) for chemotherapy alone (hazard ratio [HR], 0.87; 95 percent confidence interval [CI], 0.66-1.14; P=0.307). A prespecified analysis accounting for crossover to RYBREVANT in the chemotherapy arm showed a significant overall survival benefit with RYBREVANT plus chemotherapy, reducing the risk of death by 43 percent (HR, 0.57; 95 percent CI, 0.39-0.82; nominal P=0.003).1

Long-term follow-up provides further evidence of durable benefit, with RYBREVANT plus chemotherapy extending progression-free survival through second disease progression (PFS2) by more than 10 months compared with chemotherapy alone (28.3 vs. 17.5 months; HR, 0.59; 95 percent CI, 0.45-0.77; nominal P0.0001). Twelve percent of patients remained on first-line treatment at the clinical cutoff compared with no patients in the chemotherapy arm. Patient-reported outcomes also favored the combination, delaying the worsening of several key lung cancer symptoms compared with chemotherapy alone.1

The safety profile of IV RYBREVANT plus chemotherapy was consistent with previous reports from studies conducted before prophylactic strategies were introduced, with no new safety signals observed with longer follow-up. The most common treatment-related adverse events occurring in at least 30 percent of patients included paronychia (60 percent), neutropenia (60 percent) and rash (58 percent).1

These overall survival findings build on the primary PAPILLON analysis, which demonstrated a statistically significant and clinically meaningful 60 percent improvement in progression-free survival (primary endpoint) with first-line RYBREVANT plus chemotherapy versus chemotherapy alone in patients with EGFR exon 20 insertion mutation-positive advanced NSCLC. Clinical benefit in the primary analysis was consistent across key patient subgroups, including patients with brain metastases, EGFR exon 20 insertion variants and TP53 co-mutations. Those results, which supported global approvals of the regimen in this setting, were simultaneously published in The New England Journal of Medicine.12

Additional data presented at WCLC 2026 highlight continued innovation across RYBREVANT and RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), with approaches aimed at improving the treatment experience and helping patients stay on treatment longer. This includes prophylactic strategies in the COPERNICUS study (Abstract #MO12.09) designed to reduce key treatment-related events and subcutaneous administration evaluated in the PALOMA-2 study (Abstract #PT2.03.06).

About the PAPILLON study

PAPILLON (NCT04538664), which enrolled 308 patients, is a randomized, open-label Phase 3 study evaluating the efficacy and safety of RYBREVANT in combination with chemotherapy, compared with chemotherapy alone, in newly diagnosed patients with advanced or metastatic non-small cell lung cancer characterized by EGFR exon 20 insertion mutations. The primary endpoint of the study is progression-free survival (PFS) (using RECIST v1.1 guidelines†) as assessed by blinded independent central review (BICR). Secondary endpoints include overall response rate (ORR), PFS after first subsequent therapy, time to symptomatic progression and overall survival. Patients who received chemotherapy alone were allowed to receive RYBREVANT monotherapy in the second-line setting after confirmation of disease progression.

Patients randomized to chemotherapy alone were permitted to cross over to receive second-line RYBREVANT monotherapy after disease progression confirmed by BICR, reflecting the study's crossover design for patients in the control arm.13

About non-small cell lung cancer

Worldwide, lung cancer is one of the most common cancers, with non-small cell lung cancer (NSCLC) making up 80 to 85 percent of all lung cancer cases.14,15 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.16 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.17 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.14,15,18,19,20,21 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.22 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.23,24 EGFR exon 20 insertion mutations are the third-most prevalent activating EGFR mutation.2 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.25

About RYBREVANT FASPRO and RYBREVANT

RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) received U.S. FDA approval in December 2025 and is approved in multiple markets worldwide for the treatment of adults with EGFR-mutated non-small cell lung cancer (NSCLC), including those with exon 19 deletions, exon 21 L858R substitution mutations, and exon 20 insertion mutations. It is the only subcutaneous therapy approved for these EGFR-mutated NSCLC populations and may be used as monotherapy or in combination with LAZCLUZE® (lazertinib) or chemotherapy, depending on the specific mutation and treatment setting. For eligible patients, RYBREVANT FASPRO offers a once-monthly dosing option following initial weekly dosing. RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.

RYBREVANT FASPRO is approved in the U.S. for the same indications as intravenous RYBREVANT (amivantamab-vmjw) across multiple markets. RYBREVANT is a first-in-class, fully human bispecific antibody targeting EGFR and MET, designed to inhibit tumor growth while engaging the immune system.

The effectiveness of RYBREVANT FASPRO is supported by the established clinical profile of RYBREVANT, including data from multiple Phase 3 studies such as MARIPOSA, which demonstrated improvements in progression-free and overall survival when used in combination with LAZCLUZE in first-line advanced EGFR-mutated NSCLC.