Median overall survival, a secondary endpoint, reached nearly 3.5 years with Johnson & Johnson's RYBREVANT® plus LAZCLUZE® in atypical EGFR-mutated disease
Consistent responses observed across atypical EGFR mutation subgroups, including those historically associated with poorer outcomes
ASCO 2026 results reinforce the significance of RYBREVANT®-based regimens for patients across EGFR mutations
CHICAGO, May 29, 2026 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced updated results from the Phase 1/1b CHRYSALIS-2 study evaluating intravenous RYBREVANT® (amivantamab-vmjw) in combination with LAZCLUZE® (lazertinib) in patients with advanced non-small cell lung cancer (NSCLC) with atypical epidermal growth factor receptor (EGFR) mutations. The analysis showed encouraging long-term outcomes with RYBREVANT® plus LAZCLUZE® in this difficult-to-treat population. Median overall survival, a secondary endpoint, was nearly 3.5 years.1 The primary endpoint of objective response rate was previously reported.2 These results add to the growing body of evidence demonstrating the potential of RYBREVANT® plus LAZCLUZE® to deliver durable survival outcomes across both common and atypical EGFR-mutated advanced NSCLC in the first-line setting. Data were presented in an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8501).1
Significant unmet need in patients with atypical EGFR-mutated NSCLC
Patients with atypical EGFR-mutated NSCLC tend to have poorer outcomes than those with common EGFR mutations (exon 19 deletions and L858R substitutions), and effective first-line treatment options remain limited.3,4 These mutations represent approximately 10-20 percent of all EGFR-mutated cases.5 Median overall survival with current standard of care single-agent therapies remains under two years, highlighting a significant unmet need for treatments that can deliver more durable benefit in this setting.6,7 RYBREVANT® is designed to dual target EGFR and mesenchymal-epithelial transition (MET), while engaging the immune system.8,9,10,11 These complementary mechanisms play a central role in tumor growth and treatment resistance and may help address the underlying drivers of disease.
Expert and company perspectives supporting the strength of RYBREVANT® plus LAZCLUZE®
"For patients with non-small cell lung cancer harboring atypical EGFR-mutations, first-line treatment decisions are often clouded by uncertainty regarding the efficacy of currently available EGFR tyrosine kinase inhibitors," said Joel Neal,* M.D., Ph.D., principal investigator of the Phase 1/1b CHRYSALIS-2 study. "The responses we've seen in this trial suggest the potential for more durable disease control, and the overall survival data reinforce that picture. These long-term outcomes begin to change how we think about treatment options in managing this subtype of lung cancer." Neal is also a Professor of Medicine in the Division of Oncology at Stanford Medicine.
"Disease progression and molecular resistance remain critical barriers in EGFR-mutated non-small cell lung cancer," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "RYBREVANT-based combinations demonstrate the power of changing the biology by addressing multiple disease drivers from the start rather than relying on single-pathway strategies. With strong outcomes across all known EGFR mutations, this approach is raising the bar for what first-line treatment can achieve."
Detailed CHRYSALIS-2 study results
In Cohort C of the CHRYSALIS-2 study, RYBREVANT® plus LAZCLUZE® was evaluated as a first-line treatment in patients with atypical EGFR-mutated advanced NSCLC, excluding EGFR exon 20 insertion mutations (n=49). The most common atypical EGFR mutations included G719X (55 percent), S768X (27 percent) and L861X (24 percent), with 35 percent of patients harboring multiple atypical mutations. The study previously reported an objective response rate of 57 percent (primary endpoint).1,2
Median overall survival with RYBREVANT® plus LAZCLUZE® reached nearly 3.5 years (41.0 months; 95 percent confidence interval [CI], 27.7-not estimable) at a median follow-up of 31.3 months. Overall survival rates were 55 percent at three years and 46 percent at four years.1
Consistent clinical activity was observed across atypical EGFR mutation subgroups, as well as across patient and disease characteristics such as central nervous system metastases and TP53 status. Patients were also able to remain on treatment long-term across mutation groups and baseline characteristics. Notably, 41 percent of patients remained on RYBREVANT® for two years or longer, further supporting the durable survival observed with this combination.1
The safety profile of RYBREVANT® plus LAZCLUZE® was consistent with previous reports, with no new safety signals observed with longer follow-up. Most adverse events were Grade 1 or 2. The most common treatment-emergent adverse events occurring in more than 30 percent of patients included paronychia (78 percent), rash (65 percent), hypoalbuminemia (61 percent) and infusion-related reactions (61 percent).1
RYBREVANT®-based regimens are approved for patients with EGFR-mutated advanced NSCLC across common (exon 19 deletions and exon 21 L858R substitution mutations) and exon 20 insertion mutations, including in the first-line setting.12 These results further define long-term outcomes with first-line RYBREVANT® plus LAZCLUZE® for patients with atypical EGFR mutations. Additional data being presented at ASCO 2026 in lung, head and neck, and colorectal cancers underscore the broader potential of RYBREVANT® across tumor types.
About the CHRYSALIS-2 Study
CHRYSALIS-2 (NCT04077463) is an open-label Phase 1/1b study to evaluate the safety and pharmacokinetics of LAZCLUZE®, a third-generation EGFR-TKI, as monotherapy or in combinations with RYBREVANT®, a human bispecific EGFR and cMet antibody in participants with advanced NSCLC. The study enrolled 460 patients with advanced NSCLC.13
Cohort C of the ongoing CHRYSALIS-2 study evaluates patients with atypical EGFR-mutated advanced NSCLC, excluding exon 20 insertion and classical EGFR mutations, who are treatment-naïve or have received up to two prior lines of therapy. Patients received intravenous RYBREVANT® in combination with LAZCLUZE® administered orally once daily.13
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.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.25 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.26
About 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 in these populations and can be used as monotherapy or in combination with LAZCLUZE® (lazertinib) or chemotherapy in the front- and second-line settings, offering convenient monthly† or bi-weekly dosing. RYBREVANT FASPRO™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.
RYBREVANT® (amivantamab-vmjw), administered intravenously, received U.S. FDA approval in March 2024 and is approved for the same indications as RYBREVANT FASPRO™ across multiple markets. RYBERVANT® 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.
The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)‡ 27 include amivantamab-vmjw (RYBREVANT®) across its FDA-approved treatment settings, including as a Category 1 preferred option in combination with lazertinib (LAZCLUZE®) for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO™) may be substituted for IV amivantamab-vmjw (RYBREVANT®) where appropriate. See the latest NCCN Guidelines® for NSCLC for complete information.§ ||
The NCCN Guidelines for Central Nervous System Cancers also include amivantamab (RYBREVANT®)-based regimens, including in combination with lazertinib (LAZCLUZE®), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases.§ ||
Beyond NSCLC, RYBREVANT-based therapies are being investigated across other solid tumors, including head and neck and colorectal cancers.
The legal manufacturer for RYBREVANT® is Janssen Biotech, Inc. For more information, visit www.rybrevanthcp.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 2023.28
The legal manufacturer for LAZCLUZE® is Janssen Biotech, Inc. and Yuhan Corporation.
INDICATIONS
RYBREVANT® (amivantamab-vmjw) is indicated:
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.
in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.
in combination with 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.
as a single agent 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.
IMPORTANT SAFETY INFORMATION FOR RYBREVANT FASPRO™ AND RYBREVANT® 12,29
CONTRAINDICATIONS
RYBREVANT FASPRO™ is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Administration-Related Reactions with RYBREVANT FASPRO™
RYBREVANT FASPRO™ can cause hypersensitivity and administration-related reactions (ARR); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade ARR occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARR, 89% occurred with the initial dose (Week 1, Day 1).
Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT FASPRO™ as recommended. Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO™ injection if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO™ based on severity.
Infusion-Related Reactions with RYBREVANT®
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®
In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT® in 4.5% of patients.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population (n=281), IRRs occurred in 50% of patients including Grade 3 (3.2%) adverse reactions. IRR-related infusion modifications occurred in 46%, and permanent discontinuation of RYBREVANT® in 2.8% of patients.
RYBREVANT® as a Single Agent
In CHRYSALIS (n=302), IRRs occurred in 66% of patients. IRRs occurred in 65% of patients on Week 1 Day 1, 3.4% on Day 2 infusion, 0.4% with Week 2 infusion, and were cumulatively 1.1% with subsequent infusions. 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. IRR-related infusion modifications occurred in 62%, and permanent discontinuation of RYBREVANT® in 1.3% of patients.
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 IRRs. Monitor patients for signs and symptoms of IRRs 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 FASPRO™ and RYBREVANT® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, ILD/pneumonitis occurred in 6% of patients, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9% of patients. 5% of patients permanently discontinued RYBREVANT FASPRO™ and LAZCLUZE® due to ILD/pneumonitis.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case 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% of patients 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, 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). Immediately withhold RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® (when applicable) in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use with LAZCLUZE®
RYBREVANT FASPRO™ and RYBREVANT® in combination with LAZCLUZE® can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of treatment.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade VTE occurred in 11% of patients and 1.5% were Grade 3. 80% (n=164) of patients received prophylactic anticoagulation at study entry, with an all Grade VTE incidence of 7%. In patients who did not receive prophylactic anticoagulation (n=42), all Grade VTE occurred in 17% of patients. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO™ and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390).
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), VTEs occurred in 36% of patients 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 FASPRO™ or RYBREVANT® and LAZCLUZE® based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO™ or 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 FASPRO™ or RYBREVANT®. Treatment can continue with LAZCLUZE® at the same dose level at the discretion of the healthcare provider. Refer to the LAZCLUZE® Prescribing Information for recommended LAZCLUZE® dosage modification.
Dermatologic Adverse Reactions
RYBREVANT FASPRO™ and RYBREVANT® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus and dry skin.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, rash occurred in 80% of patients, including Grade 3 in 17% and Grade 4 in 0.5% of patients. Rash leading to dose reduction occurred in 11% of patients, and RYBREVANT FASPRO™ was permanently discontinued due to rash in 1.5% of patients.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, rash occurred in 86% of patients, 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, 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, including Grade 3 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% and permanent discontinuation due to rash occurred in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%).
When initiating treatment with RYBREVANT FASPRO or RYBREVANT and LAZCLUZE, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.
If skin reactions develop, administer supportive care including 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 FASPRO™ or RYBREVANT® in combination with LAZCLUZE®, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT FASPRO™ or RYBREVANT® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® based on severity
Hepatotoxicity
LAZCLUZE® in combination with amivantamab can cause severe hepatotoxicity (including increased ALT and AST).
RYBREVANT® with LAZCLUZE®
In MARIPOSA, based on adverse reaction data, hepatotoxicity occurred in 49% of patients treated with LAZCLUZE®, including Grade 3 in 9.3% of patients and Grade 4 in 0.5%. LAZCLUZE® was interrupted for an adverse reaction of hepatotoxicity in 8% of patients, the dose was reduced in 1.4% and permanently discontinued in 0.2%.
Perform liver function tests (including ALT, AST, and total bilirubin) before initiation of LAZCLUZE® and during treatment, as clinically indicated. Withhold, reduce the dose, or permanently discontinue LAZCLUZE® and amivantamab based on severity.
Ocular Toxicity
RYBREVANT FASPRO™ and RYBREVANT® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus and uveitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, all Grade ocular toxicity occurred in 13% of patients, including 0.5% Grade 3.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, ocular toxicity occurred in 16% of patients. 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. All events were Grade 1-2.
Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® and continue LAZCLUZE® based on severity.
Embryo-Fetal Toxicity
Based on animal models, RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE® can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO™ and RYBREVANT®. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT FASPRO™ or RYBREVANT®, and for 3 weeks after the last dose of LAZCLUZE®.
ADVERSE REACTIONS
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), the most common adverse reactions (≥20%) were rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), diarrhea (22%), vomiting (22%), constipation (22%), decreased appetite (22%), and headache (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocyte count (6%), decreased sodium (5%), decreased potassium (5%), decreased albumin (4.9%), increased alanine aminotransferase (3.4%), decreased platelet count (2.4%), increased aspartate aminotransferase (2%), increased gammaglutamyl transferase (2%), and decreased hemoglobin (2%).
Serious adverse reactions occurred in 33% of patients, with those occurring in ≥2% of patients including ILD/pneumonitis (6%); and pneumonia, VTE and fatigue (2.4% each). Death due to adverse reactions occurred in 5% of patients treated with RYBREVANT FASPRO™, including ILD/pneumonitis (1.9%), pneumonia (1.5%), and respiratory failure and sudden death (1% each).
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (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%), and nausea (21%). 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 ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT®) (2.1% each). Fatal ARs occurred in 7% of patients 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
In MARIPOSA-2 (n=130), the most common ARs (≥20%) were rash (72%), IRRs (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 ARs occurred in 32% of patients, with those occurring in >2% of patients including dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and PE (2.3%). Fatal ARs occurred in 2.3% of patients; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).
In PAPILLON (n=151), the most common ARs (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), IRRs (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 ARs occurred in 37% of patients, with those occurring in ≥2% of patients including rash, pneumonia, ILD, PE, 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
In CHRYSALIS (n=129), the most common ARs (≥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 ARs occurred in 30% of patients, with those occurring in ≥2% of patients including PE, 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 see full Prescribing Information for RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE®.
cp-491009v2
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 www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.
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 RYBREVANT®-based regimens. 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 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 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 filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.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.
###
* Joel W. Neal, M.D., Ph.D., has served as a consultant to Johnson & Johnson; he has not been paid for any media work.
† Once monthly after weekly injections from weeks 1-4.
‡ 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 specific commercially available biomarker assays or commercial laboratories.
Source: Johnson & Johnson
1 Neal JW, et al. Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced NSCLC: Updated results from the CHRYSALIS-2 study. Presented at: 2026 ASCO Annual Meeting; 2026; Chicago, IL.
2 Tomasini P, Wang Y, Li Y, et al. Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2. J Clin Oncol. 2026;44(1):54-65. doi:10.1200/JCO-24-02835
3 Kim EY, Cho EN, Park HS, et al. Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol Ther. 2016;17(3):237-245. doi:10.1080/15384047.2016.1139235
4 Patil T, Mushtaq R, Marsh S, et al. Clinicopathologic characteristics, treatment outcomes, and acquired resistance patterns of atypical EGFR mutations and HER2 alterations in stage IV non-small-cell lung cancer. Clin Lung Cancer. 2020;21(3):e191-e204. doi:10.1016/j.cllc.2019.11.008
5 Fabrizio FP, Attili I, de Marinis F. Uncommon and Rare EGFR Mutations in Non-Small Cell Lung Cancer Patients with a Focus on Exon 20 Insertions and the Phase 3 PAPILLON Trial: The State of the Art. Cancers. 2024; 16(7):1331. https://doi.org/10.3390/cancers16071331
6 Yang JC, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015;16(7):830-838. doi:10.1016/S1470-2045(15)00026-1
7 GILOTRIF® (afatinib tablets), for oral use [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc.; 2022.
8 Moores SL, Chiu ML, Bushey BS, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res. 2016;76(13):3942-3953. doi:10.1158/0008-5472.CAN-15-2833
9 Vijayaraghavan S, Lipfert L, Chevalier K, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther. 2020;19(10):2044-2056. doi:10.1158/1535-7163.MCT-20-0071
10 Yun J, Lee SH, Kim SY, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020;10(8):1194-1209. doi:10.1158/2159-8290.CD-20-0116
11 Asia-Pacific practical consensus in the management of adverse events related to amivantamab-based therapies in non-small cell lung cancer. Lung Cancer. Published online May 22, 2026. doi:10.1016/S0169-5002(26)00466-6.
12 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
13 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed May 2026.
14 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed May 2026.
15 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed May 2026.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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 May 2026.
23 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.
24 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.
25 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.
26 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.
27 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2026 © 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 May 2026.
28 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.
29 LAZCLUZE® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
Media contact: | Investor contact: |
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-demonstrates-prolonged-clinical-benefit-as-a-first-line-treatment-for-atypical-egfr-mutated-non-small-cell-lung-cancer-302785924.html