Osimertinib mesylate

Median overall survival improvement projected to exceed one year with much-anticipated overall survival analysis showing statistically superior result versus osimertinib Preventative dermatologic regimen meets primary endpoint and enhances patient experience RARITAN, N.J., March 20, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) announced today that new data from its industry-leading oncology pipeline will be presented at the 2025 European Lung Cancer Congress (ELCC), including overall survival (OS) results from the Phase 3 MARIPOSA study evaluating RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) versus osimertinib in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. "Patients with EGFR-mutated non-small cell lung cancer deserve to live longer and with more hope than current treatments provide," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. "These newest and compelling overall survival data for first-line treatment with RYBREVANT and LAZCLUZE are fundamentally changing treatment discussions and transforming expectations for how long patients can live." Additional presentations will feature the first data from the Phase 2 COCOON study, evaluating a simple to use and widely accessible dermatologic regimen given prophylactically to patients receiving the RYBREVANT® combination, and new results from the Phase 2 PALOMA-2 study evaluating the feasibility of switching to subcutaneous (SC) amivantamab. "We are redefining the way EGFR-mutated non-small cell lung cancer is treated with therapies that improve survival and give patients more time," said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. "The chemotherapy-free regimen of RYBREVANT plus LAZCLUZE represents a major breakthrough, offering an innovative and life-extending option that can meaningfully impact lives." ELCC 2025 Presentation Highlights: OS results from the Phase 3 MARIPOSA study comparing RYBREVANT® plus LAZCLUZE™ versus osimertinib in first-line EGFR-mutant advanced NSCLC (Proffered Paper Abstract #4O). First presentation of data from the Phase 2 COCOON study evaluating an easy-to-use, readily available prophylactic regimen for the prevention of dermatologic reactions in the first-line treatment of EGFR-mutant advanced NSCLC in patients receiving RYBREVANT® plus LAZCLUZE™ (Mini Oral Abstract #10MO). Initial results from the Phase 2 PALOMA-2 study evaluating switching to SC amivantamab among patients benefitting from IV delivery in advanced EGFR-mutated NSCLC (Poster Abstract #58P). Insights from the Phase 1/1b CHRYSALIS-2 study comparing RYBREVANT® plus LAZCLUZE™ to EGFR tyrosine kinase inhibitor (TKI) monotherapy in a matched real-world cohort of atypical EGFR-mutated advanced NSCLC (Poster Abstract #59P). Preliminary results from a Phase 1 study evaluating the safety and feasibility of JNJ-1900 (NBTXR3), a novel radioenhancer activated by radiation therapy, in combination with anti-PD1 treatment for patients with advanced solid tumors and lung metastases (Poster Abstract #255P). A complete list of Johnson & Johnson-sponsored abstracts is available on JNJ.com. About RYBREVANT® RYBREVANT® (amivantamab-vmjw), a fully-human bispecific 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.1 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. RYBREVANT® is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-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 first-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. In February 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of SC amivantamab and LAZCLUZE™ in Europe for the first-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. 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 first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.2†‡ Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.2 †‡ Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC.2 †‡ 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.2 †‡ 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 first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations.3 The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy 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.4 The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.5 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.6 The Phase 2 PALOMA-2 (NCT05498428) study assessing SC amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.7 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.8 The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.9 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.10 The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.11 The Phase 1/2 swalloWTail (NCT06532032) study assessing RYBREVANT® and docetaxel combination therapy in patients with metastatic NSCLC.12 The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.13 The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT® in combination with LAZCLUZE™ in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.14 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.15 The Phase 2 COCOON (NCT06120140) study assessing the effectiveness of a proactive dermatologic management regimen given with first-line RYBREVANT® and LAZCLUZE™ in patients with EGFR-mutated advanced NSCLC.16 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 efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.17 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.18,19 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.20 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.21 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.18,19,22,23,24,25 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.26 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.27,28 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.29 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.30 IMPORTANT SAFETY INFORMATION1,31 WARNINGS AND PRECAUTIONS Infusion-Related Reactions RYBREVANT® can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, 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 modifications 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 modifications 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 modifications 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 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 confirmed. 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 confirmed. 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, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first 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 first 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 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 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 findings 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 effective contraception during treatment and for 3 months after the last dose of RYBREVANT®. Advise females of reproductive potential to use effective contraception during treatment with LAZCLUZE™ and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective 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%). 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 effusion 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 specified (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 fibrillation (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 specified. 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. Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and Janssen-Cilag, S.A. are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of amivantamab or lazertinib. 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 materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC, Janssen-Cilag, S.A. and/or 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 difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behaviour 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 filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov, http://www.jnj.com, or on request from Johnson & Johnson. None of Janssen-Cilag International NV, Janssen & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC, Janssen-Cilag, S.A. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. †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 specific commercially available biomarker assays or commercial laboratories. §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. 1 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.2 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 March 2025.3 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 March 2025.4 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 March 2025. 5 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 March 2025.6 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 March 2025.7 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 March 2025.8 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 March 2025.9 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed March 2025.10 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 March 2025.11 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 March 2025.12 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. Accessed March 2025.13 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. Accessed March 2025.14 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed March 2025.15 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. Accessed March 2025.16 ClinicalTrials.gov. Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (COCOON). https://www.clinicaltrials.gov/study/NCT06120140. Accessed March 2025.17 Cho BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217.18 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed March 2025.19 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed March 2025.20 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.0b013e3182779d18.21 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.22 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. 37:97-104.23 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.24 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):78985-78993.25 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):2892-2911.26 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 March 2025.27 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.28 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65.29 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):220-9.30 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 31 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. Media contacts: Investor contact: Oncology Media Relations Lauren Johnson oncology_media_relations@its.jnj.com investor-relations@its.jnj.com 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-significantly-outperforms-standard-of-care-in-first-line-egfr-mutated-lung-cancer-with-compelling-new-data-at-elcc-2025-302406501.html SOURCE Johnson & Johnson

AstraZeneca recently launched the phase 3 Tropion-Lung15 trial—testing Datroway either by itself or with Tagrisso—in post-Tagrisso EGFR-mutated non-small cell lung cancer. As AstraZeneca awaits an FDA decision for its Daiichi Sankyo-partnered Datroway in EGFR-mutated non-small cell lung cancer (NSCLC), the British pharma has rolled out early data from a trial combining the antibody-drug conjugate (ADC) with its old blockbuster Tagrisso.A combination of Datroway and Tagrisso induced a response in 36% of patients with EGFR-mutant NSCLC who had progressed on first-line Tagrisso, new data show.The data come from module 10 of the phase 2 Orchard trial, a platform study of novel combinations in the post-Tagrisso setting. The findings are part of an abstract set to be presented at the European Lung Cancer Congress (ELCC) next week.The 36% objective response rate (ORR) was recorded among 33 evaluable patients who received Datroway at 6 milligrams per kilogram of body weight, which is the recommended dose for the TROP2-directed ADC’s FDA-approved indication in third-line HR-positive, HER2-negative breast cancer.Among 35 patients who received Datroway at a lower 4 mg/kg dose, investigators recorded a 43% ORR for the combination. The two patient groups had similar follow-up times at about 13 months.Considering the overall benefit-risk profiles of the two doses, investigators recommended the 6 mg/kg option, according to the abstract.In October, AZ and Daiichi launched the phase 3 Tropion-Lung15 trial testing Datroway 6 mg/kg—either by itself or with Tagrisso—in post-Tagrisso EGFR-mutant NSCLC. The study bears an estimated primary completion date in June 2026.Cancer that becomes resistant to Tagrisso may still have tumor cells that harbor EGFR mutations, an AstraZeneca spokesperson explained in offering the company’s rationale for adding Tagrisso to Datroway in second-line treatment.“Continuing Tagrisso ensures ongoing inhibition against those EGFRm-driven tumor cells, while also receiving treatment to suppress the resistance and, ultimately, prolong patients’ responses to treatment,” the spokesperson said in a statement. Besides the ORR measure, the higher dose of Datroway can trigger a response faster and keep tumors at bay longer, investigators found. The median time to onset of response was 1.4 months versus 2.7 months, respectively, for the two doses. Investigators estimated that only 15% of patients who received the lower dose would remain in response at nine months, whereas 64% on the preferred dose could enjoy that status.Patients on the higher Datroway dose went a median 11.7 months without disease progression, compared with 9.5 months among recipients of the lower dose, the data show.As expected, the combination with the higher dose was linked to more adverse events, although no new safety signals emerged.Overall, 56% and 34% of patients given the high and low doses, respectively, experienced grade 3 or above treatment-related adverse events. Adverse events leading to Datroway dose reductions were recorded in 59% and 23% of patients in the two groups, respectively.Interstitial lung disease or pneumonitis, a side effect that experts are watching closely for all ADCs based on Daiichi’s DXd platform, was seen in 15% of patients on the high dose, including 6% at grade 3 or above.Before the latest Datroway-Tagrisso combo readout, AZ and Daiichi have applied for FDA approval of Datroway as a monotherapy in previously treated EGFR-mutated NSCLC. A decision from the agency is expected by July 12, 2025.That submission was based on a pooled analysis of certain patients from the phase 3 Tropion-Lung01 and the phase 2 Tropion-Lung05 trials. Among 117 patients with EGFR-mutated NSCLC who had tried a median of three prior lines of therapy, Datroway alone achieved an ORR of 43% in the analysis, with the responses lasting for a median of seven months. For years, Tagrisso has been the standard first-line treatment for EGFR-mutated NSCLC. But that status has recently come under attack from Johnson & Johnson’s combination of Rybrevant and Lazcluze. Rybrevant, an EGFRxMET bispecific antibody, is also approved in combination with chemotherapy following treatment with an EGFR inhibitor such as Tagrisso.In the phase 3 Mariposa-2 trial conducted in post-Tagrisso patients, the Rybrevant-chemo regimen registered a 53% ORR, with a 6.9-month duration of response. The combo significantly reduced the risk of progression or death by 52% versus chemo alone. The median progression-free survival for the combo was 6.3 months.The latest Orchard data for AZ’s Datroway-Tagrisso cocktail look competitive, with the inherent drawbacks of cross-trial comparisons in mind. Other data at ELCCBesides Orchard, AZ also shared the primary analysis of the phase 2 Savannah trial, which evaluated Tagrisso in tandem with Hutchmed-partnered MET inhibitor savolitinib, which is approved in China under the brand name Orpathys. The analyzed patients had EGFR-mutant NSCLC with high MET overexpression or amplification following treatment with first-line Tagrisso.The combo logged a 56% ORR by investigator assessment or 55% by blinded central review among 80 patients who met a high MET expression criterion. The median duration of response was 7.1 months and 9.9 months, respectively, based on the separate types of review. And the median progression-free survival was 7.4 months and 7.5 months, respectively. The primary efficacy analysis focused on a cohort of patients who received Orpathys doses more frequently than the regimen studied as part of a 2022 readout, in which AZ reported a 49% ORR.Phase 3 results from the Saffron trial utilizing the more frequent, twice-a-day Orpathys regimen together with Tagrisso are expected in the second half of 2025. The trial includes patients who have progressed on either first- or second-line treatment with Tagrisso.Editor's Note: The story has an updated statement from AstraZeneca.