RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE® (lazertinib) prevents acquired resistance versus osimertinib in first-line EGFR-mutated non-small cell lung cancer

NEWS RELEASE RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE® (lazertinib) prevents acquired resistance versus osimertinib in rst-line EGFR-mutated non-small cell lung cancer 2025-09-06 RYBREVANT combination extends survival and signicantly reduces common EGFR and MET resistance mutations seen with osimertinib-based treatment BARCELONA, Spain, Sept. 6, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced new analyses from the Phase 3 MARIPOSA study showing that rst-line treatment with RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (lazertinib) signicantly reduces the development of epidermal growth factor receptor (EGFR)- and MET- driven resistance compared with osimertinib in patients with EGFR-mutated non-small cell lung cancer (NSCLC) with exon 19 deletion (ex19del) or L858R mutations (Poster Abstract PT1.03). These resistance data build on the combination's previously reported and unmatched overall survival benet in a chemotherapy-free regimen, which is projected to exceed four years, one year beyond the median observed with osimertinib, and underscore its potential to change the biology of the disease by preventing acquired resistance. Late-breaking results are being presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Congress on Lung Cancer (WCLC). Resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib given alone or with chemotherapy, remains a common and major barrier to long-term disease control. This ongoing challenge underscores the need for next-generation strategies that can more eectively prevent the development of resistance to EGFR and MET and extend survival for patients with EGFR-mutated lung cancer. "We now have a body of evidence that suggests TKI monotherapy is no longer enough in the rst-line treatment of ® ® ® 1 2,3 4 1 EGFR-mutated lung cancer," said Professor Sanjay Popat*, FRCP, Ph.D., medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom. "The MARIPOSA results show that combining RYBREVANT with LAZCLUZE is an important step forward, reducing EGFR- and MET-driven resistance seen with TKI- based therapy and giving patients a longer, stronger rst response." Consistent with prior data presented at the European Society for Medical Oncology (ESMO) 2024 Congress, these updated analyses from the MARIPOSA study conrm that patients treated with RYBREVANT plus LAZCLUZE were less likely to develop the two main types of resistance (MET amplication and EGFR mutations) compared to those treated with osimertinib alone. MET amplications occurred in three percent of patients on the combination versus 13 percent on osimertinib (P=0.002), and secondary EGFR mutations (such as C797S) were signicantly lower for RYBREVANT plus LAZCLUZE (1 percent vs 8 percent; P=0.01). Acquired MET amplication led to early discontinuation in 23 percent of patients on osimertinib within six months, compared with four percent on RYBREVANT plus LAZCLUZE. Among patients who stayed on the combination for at least six months, acquired resistance was rare, with two percent developing MET amplication and no EGFR C797S mutations observed. The analysis also found greater overall genetic diversity of resistance in patients treated with osimertinib, particularly among patients with EGFR- and MET-based alterations. "Choosing the rst treatment for EGFR-mutated NSCLC is one of the most important decisions we make. It can inuence how the disease progresses over time," said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Leader, Johnson & Johnson Innovative Medicine. "These data show RYBREVANT plus LAZCLUZE changes the biology of disease by blocking the resistance pathways cancers typically use to overcome treatment. By preventing resistance in the frontline, we can extend survival and keep future treatment options open for patients. These are benets not seen with prior therapies or emerging combinations." The safety prole of RYBREVANT plus LAZCLUZE was consistent with the primary analysis and no new safety signals emerged with longer-term follow-up. Most AEs (grade 3 or higher) occurred early in treatment. RYBREVANT studies suggest that using preemptive or prophylactic measures can help lower the overall number and severity of skin reactions, infusion-related reactions and venous thromboembolic events. RYBREVANT plus LAZCLUZE is approved in the United States, Europe and other markets around the world for patients with rst-line EGFR-mutated NSCLC based on the Phase 3 MARIPOSA study. About the MARIPOSA Study MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT in combination with LAZCLUZE versus osimertinib and versus LAZCLUZE alone in rst-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletion (ex19del) or 5 ® ® ® ® ® ® 1 ® ® ® 6,7,8 ® ® ® ® ® 2 substitution mutations. The primary endpoint of the study is progression-free survival (PFS) (using RECIST v1.1 guidelines**) as assessed by BICR. Secondary endpoints include overall survival, overall response rate, duration or response, progression-free survival after rst subsequent therapy (PFS2) and intracranial PFS. About RYBREVANT RYBREVANT (amivantamab-vmjw), a fully-human bispecic antibody targeting EGFR and MET with immune cell- directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the rst-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.   RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with LAZCLUZE (lazertinib) for the rst-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI. Subcutaneous amivantamab is approved in Europe in combination with LAZCLUZE for the rst-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. A Biologics License Application (BLA) was submitted to the U.S. FDA for this indication. The National Comprehensive Cancer Network(NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC prefer next-generation sequencing–based strategies over polymerase chain reaction– based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:   Amivantamab-vmjw (RYBREVANT) plus lazertinib (LAZCLUZE) as a Category 1 recommendation for rst-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.  Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for patients with 9 ®  ® 10 ® ® ® ® ® ® ® ® § ® ® 11† ‡ ® 3 locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.  Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for rst-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation- positive advanced NSCLC.  Amivantamab-vmjw (RYBREVANT) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC. RYBREVANT is being studied in multiple clinical trials in NSCLC, including:  The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with LAZCLUZE versus osimertinib and versus LAZCLUZE alone in the rst-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the ecacy of RYBREVANT (with or without LAZCLUZE) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations after disease progression on or after osimertinib. The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin- pemetrexed versus chemotherapy alone in the rst-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE with subcutaneous (SC) amivantamab compared to RYBREVANT in patients with EGFR-mutated advanced or metastatic NSCLC. The Phase 2 PALOMA-2 (NCT05498428) study assessing SC amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC. The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of SC amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for SC amivantamab delivery. The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in patients with advanced NSCLC. The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT in combination with LAZCLUZE and LAZCLUZE as a monotherapy in patients with advanced NSCLC with EGFR mutations. The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC. The Phase 1/2 swalloWTail (NCT06532032) study assessing RYBREVANT and docetaxel combination therapy in patients with metastatic NSCLC. The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC. 11 † ‡ ® 11 † ‡ ® 11 † ‡ ® ® ® ® 12 ® ® 13 ® 14 ® ® 15 16 17 ® 18 ® ® ® 19 ® 20 ® 21 ® 22 4 The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of rst- dose infusion-related reactions with RYBREVANT in combination with LAZCLUZE in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC. The Phase 2 COPERNICUS (NCT06667076) study combining developments in treatment administration and prophylactic supportive care in representative US patients with common EGFR-mutated NSCLC treated with SC amivantamab in combination with LAZCLUZE or chemotherapy. The Phase 2 COCOON (NCT06120140) study assessing the eectiveness of a proactive dermatologic management regimen given with rst-line RYBREVANT and LAZCLUZE in patients with EGFR-mutated advanced NSCLC. The legal manufacturer for RYBREVANT is Janssen Biotech, Inc. For more information, visit: https://www.RYBREVANT.com. About LAZCLUZE In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE (marketed as LECLAZA in South Korea). LAZCLUZE is an oral, third-generation, brain- penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the ecacy and safety of LAZCLUZE from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.  The legal manufacturer for LAZCLUZE is Janssen Biotech, Inc. and Yuhan Corporation. About Non-Small Cell Lung Cancer Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases. The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division. 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. EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations. The ve-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent. EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation. Patients with EGFR exon 20 insertion mutations have a real-world ve-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 ve- year OS of 19 percent. ® ® 23 ® 24 ® ® 25 ® ® ® ® ® 26 ® 27,28 29 30 27,28,31,32,33,34 35 36,37 38 39 5 IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Infusion-Related Reactions RYBREVANT can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, ushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour. RYBREVANT with LAZCLUZE RYBREVANT in combination with LAZCLUZE can cause infusion-related reactions. In MARIPOSA (n=421), IRRs occurred in 63% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of infusion modications due to IRR was 54% of patients, and IRRs leading to dose reduction of RYBREVANT occurred in 0.7% of patients. Infusion-related reactions leading to permanent discontinuation of RYBREVANT occurred in 4.5% of patients receiving RYBREVANT in combination with LAZCLUZE. RYBREVANT with Carboplatin and Pemetrexed Based on the pooled safety population (n=281), IRR occurred in 50% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT due to IRR. RYBREVANT as a Single Agent In CHRYSALIS (n=302), IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR. Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related 10,40 ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® 6 reactions. Monitor patients for signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT. Interstitial Lung Disease/Pneumonitis RYBREVANT can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. RYBREVANT with LAZCLUZE In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT and LAZCLUZE due to ILD/pneumonitis. RYBREVANT with Carboplatin and Pemetrexed Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% treated with RYBREVANT in combination with carboplatin and pemetrexed with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT due to ILD/pneumonitis. RYBREVANT as a Single Agent In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT due to ILD/pneumonitis. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). For patients receiving RYBREVANT in combination with LAZCLUZE, immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is conrmed. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is conrmed. Venous Thromboembolic (VTE) Events with Concomitant Use of RYBREVANT and LAZCLUZE RYBREVANT in combination with LAZCLUZE can cause serious and fatal venous thromboembolic (VTE) events, ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® 7 including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the rst four months of therapy. In MARIPOSA, VTEs occurred in 36% of patients receiving RYBREVANT in combination with LAZCLUZE, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE; 1% of patients had VTE leading to dose reductions of RYBREVANT, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE. The median time to onset of VTEs was 84 days (range: 6 to 777). Administer prophylactic anticoagulation for the rst four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT and LAZCLUZE based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT and LAZCLUZE at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT and continue treatment with LAZCLUZE at the same dose level at the discretion of the healthcare provider. Dermatologic Adverse Reactions RYBREVANT can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin. RYBREVANT with LAZCLUZE In MARIPOSA, rash occurred in 86% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT and 30% for LAZCLUZE, rash leading to dose reductions occurred in 23% of patients for RYBREVANT and 19% for LAZCLUZE, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT and 1.7% for LAZCLUZE. RYBREVANT with Carboplatin and Pemetrexed Based on the pooled safety population, rash occurred in 82% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® 8 occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT and 3.1% discontinued pemetrexed. RYBREVANT as a Single Agent In CHRYSALIS, rash occurred in 74% of patients treated with RYBREVANT as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT as a single agent. Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT or LAZCLUZE in combination with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin. When initiating RYBREVANT treatment with or without LAZCLUZE, administer alcohol-free emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g. use of oral antibiotics) to reduce the risk of dermatologic reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT in combination with LAZCLUZE, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT based on severity. Ocular Toxicity RYBREVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis. RYBREVANT with LAZCLUZE In MARIPOSA, ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT and continue LAZCLUZE based on severity. RYBREVANT with Carboplatin and Pemetrexed ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® ® 9 Based on the pooled safety population, ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed. All events were Grade 1 or 2. RYBREVANT as a Single Agent In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity. Embryo-Fetal Toxicity Based on its mechanism of action and ndings from animal models, RYBREVANT and LAZCLUZE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use eective contraception during treatment and for 3 months after the last dose of RYBREVANT. Advise females of reproductive potential to use eective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use eective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose. Adverse Reactions RYBREVANT with LAZCLUZE For the 421 patients in the MARIPOSA clinical trial who received RYBREVANT in combination with LAZCLUZE, the most common adverse reactions ( ≥ 20%) were rash (86%), nail toxicity (71%), infusion-related reactions (RYBREVANT, 63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), nausea (21%), and ocular toxicity (16%). The most common Grade 3 or 4 laboratory abnormalities ( ≥ 2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%). ® ® ® ® ® ® ® ® ® ® ® ® ® ® 10 Serious adverse reactions occurred in 49% of patients who received RYBREVANT in combination with LAZCLUZE. Serious adverse reactions occurring in ≥ 2% of patients included VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural eusion and infusion-related reaction (RYBREVANT) (2.1% each). Fatal adverse reactions occurred in 7% of patients who received RYBREVANT in combination with LAZCLUZE due to death not otherwise specied (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each). RYBREVANT with Carboplatin and Pemetrexed For the 130 patients in the MARIPOSA-2 clinical trial who received RYBREVANT in combination with carboplatin and pemetrexed, the most common adverse reactions ( ≥ 20%) were rash (72%), infusion-related reactions (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities ( ≥ 2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%). In MARIPOSA-2, serious adverse reactions occurred in 32% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in >2% of patients included dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and pulmonary embolism (2.3%). Fatal adverse reactions occurred in 2.3% of patients who received RYBREVANT in combination with carboplatin and pemetrexed; these included respiratory failure, sepsis, and ventricular brillation (0.8% each). For the 151 patients in the PAPILLON clinical trial who received RYBREVANT in combination with carboplatin and pemetrexed, the most common adverse reactions ( ≥ 20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities ( ≥ 2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma- glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%). In PAPILLON, serious adverse reactions occurred in 37% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥ 2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise ® ® ® ® ® ® ® ® ® ® ® 11 specied. RYBREVANT as a Single Agent For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT as a single agent, the most common adverse reactions ( ≥ 20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities ( ≥ 2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%). Serious adverse reactions occurred in 30% of patients who received RYBREVANT. Serious adverse reactions in ≥ 2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death. LAZCLUZE Drug Interactions Avoid concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4. Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate. Please read full Prescribing Information for RYBREVANT. Please read full Prescribing Information for LAZCLUZE. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com or at http://www.innovativemedicine.jnj.com/. Follow us at @JNJInnovMed.   ® ® ® ® ® ® ® 12 Cautions Concerning Forward-Looking Statements  This press release contains "forward-looking statements" as dened in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benets and treatment impact of RYBREVANT or LAZCLUZE. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing diculties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product ecacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other lings with the Securities and Exchange Commission. Copies of these lings are available online at http://www.sec.gov, http://www.jnj.com, or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.   *Professor Sanjay Popat has served as a consultant to Johnson & Johnson; he has not been paid for any media work.  **RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger. The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. See the NCCN Guidelines for detailed recommendations, including other treatment options. The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specic commercially available biomarker assays or commercial laboratories. ® ® § † ‡ 13 Source: Johnson & Johnson Hayashi, H, et al. Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA [IASLC abstract PT1.03]. Presented at: IASLC 2025 World Lung Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. 2025 European Lung Cancer Congress. March 26, 2025. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. doi:10.1097/JTO.0b013e3182779d18 Tan CS, Kumarakulasinghe NB, Huang YQ, et al. Third-generation EGFR TKIs: current data and future directions. Mol Cancer. 2018;17:29. doi:10.1186/s12943-018-0778-0. Besse B, et al. Presented at the European Society for Medical Oncology (ESMO) Congress; September 13–17, 2024; Barcelona, Spain. Girard, et al. Preventing Moderate to Severe Dermatologic Adverse Events in First-line EGFR-mutant Advanced NSCLC Treated with Amivantamab Plus Lazertinib: Early Success of the COCOON Trial. 2025 European Lung Cancer Congress. March 27, 2025. Spira AI, et al. Preventing infusion-related reactions with intravenous amivantamab—results from SKIPPirr, a phase 2 study: a brief report. J Thorac Oncol. 2025;20(6):809-816. Leighl N, et al. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. J Clin Oncol. 2024;42(30):3593-3605. ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed September 2025. RYBREVANT Prescribing Information. Horsham, PA: Janssen Biotech, Inc. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non- Small Cell Lung Cancer V.3.2025 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed September 2025.                1 2 3 4 5 6 7 8 9 10 ® 11 ® 12 13 ® 14 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed September 2025. ClinicalTrials.gov. A Study of LAZCLUZE With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non- small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecic EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed September 2025. ClinicalTrials.gov. A Study of LAZCLUZE as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed September 2025. ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032? term=Swallowtail&intr=amivantamab&rank=1. Accessed September 2025. ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734? term=polydamas&rank=1. Accessed September 2025. ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed September 2025. ClinicalTrials.gov. A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (COPERNICUS). https://www.clinicaltrials.gov/study/NCT06667076?term=COPERNICUS&rank=3. Accessed September 2025. ClinicalTrials.gov. Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib 14 15 ® 16 17 18 19 ® 20 21 22 23 24 25 15 (COCOON). https://www.clinicaltrials.gov/study/NCT06120140. Accessed September 2025. Cho BC, et al. Lazertinib versus getinib as rst-line treatment in patients with EGFR-mutated advanced non- small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed September 2025. American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung- cancer/about/what-is.html. Accessed September 2025. Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18. Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. 2021 World Conference on Lung Cancer Annual Meeting; January 29, 2021. Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor- mutant non-small cell lung cancer. J Clin Oncol. 37:97-104. Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. 2021 World Conference on Lung Cancer Annual Meeting; January 29, 2021. Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911. American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease- lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed September 2025. Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site. Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65. Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. 2021 World Conference on Lung Cancer Annual Meeting; January 29, 2021.  LAZCLUZE Prescribing Information. Horsham, PA: Janssen Biotech, Inc.   M di t t   I t t t 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 ® 16 Media contacts: Oncology Media Relations [email protected]       Investor contact: Lauren Johnson [email protected] U.S. Medical Inquiries: +1 800 526-7736     View original content to download multimedia:https://www.prnewswire.com/news-releases/rybrevant- amivantamab-vmjw-plus-lazcluze-lazertinib-prevents-acquired-resistance-versus-osimertinib-in-rst-line-egfr- mutated-non-small-cell-lung-cancer-302548296.html SOURCE Johnson & Johnson 17

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