On February 17, 2026 Johnson & Johnson (NYSE: JNJ) reported the U.S. Food and Drug Administration (FDA) has approved a new, simplified monthly dosing schedule* for RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj). When administered in combination with oral LAZCLUZE (lazertinib) for the first-line treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), monthly dosing delivers consistent outcomes with the previously approved bi-weekly subcutaneous (SC) dosing schedule.1,2
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This milestone builds upon the recent FDA approval of RYBREVANT FASPRO, which transformed administration time from hours to minutes and offers a fivefold reduction in administration-related reactions (ARRs), when compared to intravenous (IV) delivery. With this newly approved monthly dosing schedule, patients are able to transition to monthly dosing as early as Week 5. Together, these advances build on an unmatched survival benefit while supporting continued treatment optimization, further simplifying care delivery and offering greater convenience.1
"A monthly dosing schedule offers patients convenience without sacrificing efficacy," said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology & Therapeutics Research, City of Hope, and principal investigator for the PALOMA-3 and MARIPOSA studies.** "With a flexible schedule that reduces time in the clinic, patients may be able to stay on therapy longer and free up time to focus on the moments that matter most."
Recently presented at the 2025 World Conference on Lung Cancer (WCLC), PALOMA-2 data demonstrated that monthly RYBREVANT FASPRO dosing in combination with LAZCLUZE delivered a high objective response rate (ORR) in previously untreated, EGFR-mutated advanced NSCLC. The study showed significant reduction in ARRs compared to historical IV administration and consistent rates with bi-weekly SC delivery.2
"This latest milestone represents the culmination of our unwavering efforts and commitment to fundamentally redefine the way we treat patients with EGFR-mutated non-small cell lung cancer," said Mahadi Baig, M.D., M.H.C.M., Vice President, U.S. Medical Affairs, Johnson & Johnson. "Building on unmatched overall survival and regimens that support proactive side effect management, this once-monthly injection now delivers the simplest and fastest combination therapy for patients with EGFR-mutated non-small cell lung cancer."
The safety profile of monthly dosing of RYBREVANT FASPRO is comparable when it is administered every two weeks. Consistent with IV and SC administration, most adverse events were related to EGFR/MET inhibition. ARRs were consistent with the bi-weekly dosing schedule (12% vs 13% respectively) and fivefold lower when compared to historical IV administration (66%). Similarly, venous thromboembolic events (VTEs) were consistent with bi-weekly SC administration (13% vs 11% with anticoagulation) and lower than historic IV data without anticoagulation (38%).1,2
No new safety signals were identified. Only 8% of patients discontinued amivantamab due to treatment-related adverse events. The mean plasma concentration levels were consistent with historical IV and bi-weekly SC dosing data, supporting pharmacokinetic comparability.2
Access to RYBREVANT FASPRO
Johnson & Johnson offers comprehensive access and support information and resources to assist patients in gaining access to RYBREVANT FASPRO. Our patient support program, RYBREVANT withMe†, is available to provide personalized support to help patients start and stay on their Johnson & Johnson medicines. RYBREVANT withMe helps providers support their patients by verifying patients’ insurance coverage, providing information on Prior Authorization and Appeals processes and educating on reimbursement processes. Patients can connect to RYBREVANT withMe to receive cost support, regardless of insurance type, free, personalized one-on-one support from a Care Navigator, and resources and community connections. Learn more at RYBREVANTwithMe.com or by calling 833-JNJ-wMe1 (833-565-9631).
About the PALOMA-2 Study
PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and pharmacokinetics (PK) of first-line SC amivantamab (administered via manual injection) combined with LAZCLUZE and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. The primary endpoint was ORR as assessed by the investigator per RECIST v1.1.2,7 PALOMA-2 Cohort 5 evaluated the efficacy, PK, and safety of first-line SC amivantamab Q4W plus LAZCLUZE in EGFR-mutated NSCLC.
About the MARIPOSA Study
MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT (amivantamab-vmjw) plus LAZCLUZE versus osimertinib and versus LAZCLUZE alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints include overall survival (OS), ORR, duration of response (DoR), progression-free survival after first subsequent therapy (PFS2) and intracranial PFS.8
Resistance to third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib (when given alone or with chemotherapy), remains a major barrier to long-term disease control.9 The combination regimen RYBREVANT plus LAZCLUZE uses a multitargeted mechanism of action: targeting EGFR mutations from two angles, blocking MET, and engaging the immune system.10 This approach has the potential to change the natural history of the disease by reducing the spectrum and complexity of acquired resistance mechanisms.11
An analysis from MARIPOSA, presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Congress on Lung Cancer (WCLC), demonstrated that the combination significantly reduced the development of EGFR- and MET-driven resistance compared with osimertinib in the first-line setting. MET amplifications occurred in three percent of patients on the combination vs 13 percent on osimertinib (P=0.002), and secondary EGFR mutations (such as C797S) were significantly lower for RYBREVANT plus LAZCLUZE (1 percent vs 8 percent; P=0.01). Notably, acquired MET amplification led to early discontinuation in 23 percent of patients on osimertinib within six months, compared with four percent on RYBREVANT plus LAZCLUZE.12,13
About RYBREVANT FASPRO and RYBREVANT
In December 2025, the U.S. FDA approved RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) across all indications of intravenous RYBREVANT (amivantamab-vmjw). This subcutaneously administered therapy is also approved in Europe, Japan, China, and other markets.
RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.
The effectiveness of RYBREVANT FASPRO has been established based on adequate and well controlled studies of RYBREVANT. Data across multiple Phase 3 studies, including MARIPOSA, have demonstrated the clinical benefit of RYBREVANT in improving PFS and OS in advanced EGFR-mutated NSCLC.
RYBREVANT is approved in the U.S., Europe and other markets across four indications in EGFR-mutated NSCLC, including two in the first-line setting and two in the second-line, for patients with either exon 19 deletions, exon 21 L858R mutations, or exon 20 insertion mutations, as monotherapy or in combination with LAZCLUZE (lazertinib) or chemotherapy.
RYBREVANT is a first-in-class, fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity.
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines)‡i include amivantamab-vmjw (RYBREVANT) across multiple treatment settings, including its recent inclusion as a NCCN Category 1 preferred option when used with lazertinib (LAZCLUZE) for first-line treatment of people with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Amivantamab and hyaluronidase-lpuj subcutaneous injection (RYBREVANT FASPRO) may be substituted for IV amivantamab-vmjw (RYBREVANT). See the latest NCCN Guidelines for NSCLC for complete information.§‖
The NCCN Guidelines for Central Nervous System Cancers also identify amivantamab-vmjw (RYBREVANT)-based regimens, including the combination with lazertinib (LAZCLUZE), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases.§‖
The legal manufacturer for RYBREVANT is Janssen Biotech, Inc. For more information, visit 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.
About Non-Small Cell Lung Cancer (NSCLC)
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.15 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.16 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.16-19 EGFR exon 19 deletions or EGFR L858R mutations are the most common EGFR mutations.20,21 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.22 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.23 Patients with EGFR exon 20 insertion mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR exon 19 deletions or L858R mutations, who have a real-world five-year OS of 19 percent.21
About EGFR Mutations
Epidermal growth factor receptor (EGFR) mutations are among the most common oncogenic drivers in NSCLC, especially in younger individuals and those who have never smoked. These mutations promote uncontrolled cell growth and are linked to poor outcomes.19 Despite progress with targeted therapies, including third-generation EGFR TKI, long-term survival remains limited, with five-year survival rates below 20 percent.22 Overcoming resistance mechanisms, such as MET amplification and secondary EGFR mutations, is essential for improving outcomes and extending survival in EGFR-mutated NSCLC.12
INDICATIONS
RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) and RYBREVANT (amivantamab-vmjw) are 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 INFORMATION1
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 (ARRs); 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 ARRs occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARRs, 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, 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, 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.
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. 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. 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 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 gamma-glutamyl 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.
(Press release, Johnson & Johnson, FEB 17, 2026, View Source [SID1234662735])