RYBREVANT ® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) present robust favorable total survival development versus osimertinib in EGFR-mutated superior lung most cancers

New longer-term information from the MARIPOSA examine verify superior outcomes of chemotherapy-free RYBREVANT ^® plus LAZCLUZE™ routine in comparison with osimertinib monotherapy as first-line remedy

Outcomes from an interim evaluation featured in late-breaker oral presentation at WCLC

SAN DIEGO, Sept. 8, 2024 /PRNewswire/ — Johnson & Johnson (NYSE: JNJ) at present introduced longer follow-up information from the landmark Section 3 MARIPOSA examine which confirmed first-line therapy with RYBREVANT ^® (amivantamab-vmjw) mixed with LAZCLUZE™ (lazertinib) supplied constant profit throughout long-term outcomes in comparison with osimertinib monotherapy in grownup sufferers with superior non-small cell lung most cancers (NSCLC) with epidermal progress issue receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. The info present a powerful and enhancing total survival (OS) development favoring RYBREVANT ^® plus LAZCLUZE™ at roughly three years of follow-up. These outcomes had been introduced in a late-breaking oral presentation on the Worldwide Affiliation for the Research of Lung Most cancers (IASLC) 2024 World Convention on Lung Most cancers (WCLC) (Summary #1146).¹

At three years (a median follow-up of 31.1 months), 61 p.c of sufferers receiving RYBREVANT ^® plus LACLUZE™ had been alive in comparison with 53 p.c of these handled with osimertinib based mostly on an evaluation carried out on the request of a well being authority (Median OS not estimable vs 37.3 months; hazard ratio [HR], 0.77; [95 percent confidence interval [CI], 0.61-0.96]; nominal P=0.019). Total survival will proceed to be assessed with long run follow-up as a key secondary endpoint. The first efficacy end result measure was progression-free survival (PFS) as assessed by blinded unbiased central assessment (BICR).¹

“By combining the multi-targeted mechanism of RYBREVANT with LAZCLUZE, a central nervous system-penetrant third-generation tyrosine kinase inhibitor, we are advancing a chemotherapy-free regimen for the first-line treatment of patients with EGFR-mutant NSCLC. This approach blocks EGFR and MET pathways and leverages the immune system, offering patients an opportunity for prolonged benefits,” mentioned Shirish M. Gadgeel, M.D., Chief of Division of Hematology and Oncology, Affiliate Director at Henry Ford (NYSE:) Most cancers Institute and presenting creator. “Even more encouraging is the marked improvement in the hazard ratio and the ongoing separation of survival curves, showing an eight percent improvement at three years for RYBREVANT plus LAZCLUZE compared to osimertinib. This supports the long-term benefit of the combination as a first-line treatment option in this setting.”

Outcomes additional confirmed RYBREVANT ^® plus LAZCLUZE™ demonstrated a development towards improved central nervous system illness management in comparison with osimertinib at three years (HR, 0.82; [95 percent CI, 0.62-1.09]; nominal P=0.165). On the three-year landmark, intracranial PFS was double for RYBREVANT ^® plus LAZCLUZE™ versus osimertinib (38 p.c vs 18 p.c, respectively). Extra sufferers remained on therapy at three years with the RYBREVANT ^® mixture in comparison with osimertinib (40 p.c vs 29 p.c, respectively; HR, 0.80; [95 percent CI, 0.68-0.96]; nominal P=0.014). Moreover, extra sufferers receiving RYBREVANT ^® and LAZCLUZE™ on the three-year follow-up had not began a subsequent remedy versus osimertinib (45 p.c vs 32 p.c, respectively; HR, 0.77; [95 percent CI, 0.65-0.93]; nominal P=0.005). Development-free survival after first subsequent remedy was 57 p.c for the RYBREVANT ^® mixture in comparison with 49 p.c for osimertinib (HR, 0.73; [95 percent CI, 0.59-0.91]; nominal P=0.004).¹

“Promising results like these presented at WCLC reinforce our mission to improve the lives of patients diagnosed with lung cancer,” mentioned Joshua Bauml, M.D., Vice President, Lung Most cancers Illness Space Stronghold Chief, Johnson & Johnson Modern Medication. “We are encouraged by the favorable overall survival trend observed with RYBREVANT plus LAZCLUZE and are eager to see how these data evolve as we continue to follow patients over time.”

As beforehand reported within the MARIPOSA examine, the protection profile was in keeping with the protection profiles of the person remedies. The speed of discontinuation of all examine remedies on account of treatment-related antagonistic occasions for RYBREVANT ^® plus LAZCLUZE™ was 10 p.c. The speed of interstitial lung illness (together with pneumonitis) was lower than three p.c in each arms.²

In August 2024, RYBREVANT ^® mixed with LAZCLUZE™ was authorised following a Precedence Evaluate by the U.S. Meals and Drug Administration as a first-line remedy for sufferers with EGFR-mutated NSCLC based mostly on the favorable efficacy and security profile demonstrated on this examine.

In regards to the MARIPOSA Research

MARIPOSA (NCT04487080), which enrolled 1,074 sufferers, is a randomized, Section 3 examine evaluating RYBREVANT ^® together with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in first-line therapy of sufferers with regionally superior or metastatic NSCLC with EGFR ex19del or L858R substitution mutations. The first endpoint of the examine is PFS (utilizing RECIST v1.1 tips) as assessed by BICR. Secondary endpoints embody OS, total response price (ORR), length of response (DOR), second progression-free survival (PFS2) and intracranial PFS.³

About RYBREVANT ^®

RYBREVANT ^® (amivantamab-vmjw), a fully-human bispecific antibody focusing on EGFR and MET with immune cell-directing exercise, is authorised within the U.S., Europe, and in different markets all over the world as monotherapy for the therapy of grownup sufferers with regionally superior or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved take a look at, whose illness has progressed on or after platinum-based chemotherapy.⁴

RYBREVANT ^® is authorised within the U.S., Europe and in markets all over the world together with chemotherapy (carboplatin and pemetrexed) for the first-line therapy of grownup sufferers with regionally superior or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved take a look at.

RYBREVANT ^® is authorised within the U.S. together with LAZCLUZE™ (lazertinib) for the first-line therapy of grownup sufferers with regionally superior or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved take a look at. A advertising authorization software (MAA) and kind II extension of indication software had been submitted to the European Medicines Company (EMA) searching for approval of LAZCLUZE™ together with RYBREVANT ^® based mostly on the MARIPOSA examine.

In November 2023, Johnson & Johnson submitted a supplemental Biologics License Utility (sBLA) to the U.S. FDA for RYBREVANT ^® together with chemotherapy for the therapy of sufferers with EGFR-mutated NSCLC who progressed on or after osimertinib based mostly on the MARIPOSA-2 examine. This indication was authorised in Europe in August 2024.

In June 2024, Johnson & Johnson submitted a BLA to the U.S. FDA for the subcutaneous formulation of RYBREVANT ^® together with LAZCLUZE™ for all presently authorised or submitted indications of intravenous (IV) RYBREVANT ^® in sure sufferers with NSCLC. A submission for the extension of the RYBREVANT ^® advertising authorization (line extension) was additionally submitted to the EMA searching for approval for this indication.

The NCCN Medical Apply Pointers in Oncology (NCCN Pointers ^®) for NSCLC ^§ desire next-generation sequencing“based mostly methods over polymerase chain response“based mostly approaches for the detection of EGFR exon 20 insertion variants. The NCCN Pointers embody:

• Amivantamab-vmjw (RYBREVANT ^®) plus chemotherapy as a most well-liked (Class 1 most well-liked advice) subsequent remedy for sufferers with regionally superior or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who skilled illness development after therapy with Osimertinib.^{5 ¡}
• Amivantamab-vmjw (RYBREVANT ^®) plus carboplatin and pemetrexed as a most well-liked (Class 1 most well-liked advice) first-line remedy in treatment-naive sufferers with newly recognized superior or metastatic EGFR exon 20 insertion mutation-positive superior NSCLC, or as a subsequent remedy choice (Class 2A advice) for sufferers which have progressed on or after platinum-based chemotherapy with or with out immunotherapy and have EGFR exon 20 insertion mutation-positive superior NSCLC.^{5 ¡}
• Amivantamab-vmjw (RYBREVANT ^®) as a subsequent remedy choice (Class 2A advice) for sufferers which have progressed on or after platinum-based chemotherapy with or with out an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.^{5 ¡}

Along with the Section 3 MARIPOSA examine, RYBREVANT ^® is being studied in a number of scientific trials in NSCLC, together with:

• The Section 3 MARIPOSA-2 (NCT04988295) examine assessing the efficacy of RYBREVANT ^® (with or with out LAZCLUZE™) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in sufferers with regionally superior or metastatic EGFR ex19del or L858R substitution NSCLC after illness development on or after osimertinib.⁶
• The Section 3 PAPILLON (NCT04538664) examine assessing RYBREVANT ^® together with carboplatin-pemetrexed versus chemotherapy alone within the first-line therapy of sufferers with superior or metastatic NSCLC with EGFR exon 20 insertion mutations.⁷
• The Section 3 PALOMA-3 (NCT05388669) examine assessing LAZCLUZE™ with subcutaneous amivantamab in comparison with intravenous amivantamab in sufferers with EGFR-mutated superior or metastatic NSCLC.⁸
• The Section 2 PALOMA-2 (NCT05498428) examine assessing subcutaneous amivantamab in sufferers with superior or metastatic stable tumors together with EGFR-mutated NSCLC.⁹
• The Section 1 PALOMA (NCT04606381) examine assessing the feasibility of subcutaneous administration of amivantamab based mostly on security and pharmacokinetics and to find out a dose, dose routine and formulation for amivantamab subcutaneous supply.¹⁰
• The Section 1 CHRYSALIS (NCT02609776) examine evaluating RYBREVANT ^® in sufferers with superior NSCLC.¹¹
• The Section 1/1b CHRYSALIS-2 (NCT04077463) examine evaluating RYBREVANT ^® together with LAZCLUZE™ and LAZCLUZE™ as a monotherapy in sufferers with superior NSCLC with EGFR.¹²
• The Section 1/2 METalmark (NCT05488314) examine assessing RYBREVANT ^® and capmatinib mixture remedy in regionally superior or metastatic NSCLC.¹³
• The Section 1/2 PolyDamas (NCT05908734) examine assessing RYBREVANT ^® and cetrelimab mixture remedy in regionally superior or metastatic NSCLC.¹⁴
• The Section 2 SKIPPirr examine (NCT05663866) exploring methods to lower the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT ^® together with LAZCLUZE™ in relapsed or refractory EGFR-mutated superior or metastatic NSCLC.¹⁵
• The Section 1/2 swalloWTail (NCT06532032) examine assessing RYBREVANT ^® and docetaxel mixture remedy in sufferers with metastatic NSCLC.¹⁶
• The Section 1b/2 OrigAMI-1 (NCT05379595) examine assessing RYBREVANT ^® monotherapy and along with standard-of-care chemotherapy in sufferers with superior or metastatic colorectal most cancers.¹⁷
• The Section 1b/2 OrigAMI-4 (NCT06385080) examine assessing RYBREVANT ^® monotherapy and along with standard-of-care therapeutic brokers in sufferers with recurrent/metastatic head and neck squamous cell carcinoma.¹⁸

For extra data, go to: https://www.RYBREVANT.com.

About LAZCLUZE™

In 2018, Janssen Biotech, Inc., entered right into a license and collaboration settlement with Yuhan Company for the event of LAZCLUZE™ (marketed as LACLAZA in Korea). LAZCLUZE™ is an oral, third-generation, brain-penetrant EGFR TKI that targets each the T790M mutation and activating EGFR mutations whereas sparing wild-type EGFR. An evaluation of the efficacy and security of LAZCLUZE™ from the Section 3 LASER301 examine was printed in The Journal of Medical Oncology in 2023.

About Non-Small Cell Lung Most cancers

Worldwide, lung most cancers is likely one of the most typical cancers, with NSCLC making up 80 to 85 p.c of all lung most cancers circumstances.^19,20 The primary subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and huge cell carcinoma.²¹ Among the many most typical driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell progress and division.²²EGFR mutations are current in 10 to fifteen p.c of Western sufferers with NSCLC with adenocarcinoma histology and happen in 40 to 50 p.c of Asian sufferers.^{21,22,23,24,25,26}EGFR ex19del or EGFR L858R mutations are the commonest EGFR mutations.²⁷ The five- yr survival price for all individuals with superior NSCLC and EGFR mutations handled with EGFR tyrosine kinase inhibitors (TKIs) is lower than 20 p.c.^28,29 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.³⁰ Sufferers with EGFR exon 20 insertion mutations have a real-world five-year total survival (OS) of eight p.c within the frontline setting, which is worse than sufferers with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 p.c.³¹

IMPORTANT SAFETY INFORMATION^4,32

WARNINGS AND PRECAUTIONS

Infusion-Associated Reactions

RYBREVANT ^® could cause infusion-related reactions (IRR); indicators and signs of IRR embody dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is roughly 1 hour.

RYBREVANT ^® with LAZCLUZE™

RYBREVANT ^® together with LAZCLUZE™ could cause infusion-related reactions. In MARIPOSA (n=421), IRRs occurred in 63% of sufferers handled with RYBREVANT ^® together with LAZCLUZE™, together with Grade 3 in 5% and Grade 4 in 1% of sufferers. The incidence of infusion modifications on account of IRR was 54% of sufferers, and IRRs resulting in dose discount of RYBREVANT ^® occurred in 0.7% of sufferers. Infusion-related reactions resulting in everlasting discontinuation of RYBREVANT ^® occurred in 4.5% of sufferers receiving RYBREVANT ^® together with LAZCLUZE™.

RYBREVANT ^® with Carboplatin and Pemetrexed

In PAPILLON (n=151), infusion-related reactions occurred in 42% of sufferers handled with RYBREVANT ^® together with carboplatin and pemetrexed, together with Grade 3 (1.3%) antagonistic reactions. The incidence of infusion modifications on account of IRR was 40%, and 0.7% of sufferers completely discontinued RYBREVANT ^®.

RYBREVANT ^® as a Single Agent

In CHRYSALIS (n=302), IRR occurred in 66% of sufferers handled with RYBREVANT ^®. Amongst sufferers receiving therapy on Week 1 Day 1, 65% skilled an IRR, whereas 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% had been Grade 1-2, 2.2% had been Grade 3, and 0.4% had been Grade 4. The median time to onset was 1 hour (vary 0.1 to 18 hours) after begin of infusion. The incidence of infusion modifications on account of IRR was 62% and 1.3% of sufferers completely discontinued RYBREVANT ^® on account of IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT ^® as advisable. Administer RYBREVANT ^® through a peripheral line on Week 1 and Week 2 to cut back the danger of infusion-related reactions. Monitor sufferers for indicators and signs of infusion reactions throughout RYBREVANT ^® infusion in a setting the place cardiopulmonary resuscitation treatment and tools can be found. Interrupt infusion if IRR is suspected. Scale back the infusion price or completely discontinue RYBREVANT ^® based mostly on severity.

Interstitial Lung Illness/Pneumonitis

RYBREVANT ^® could cause extreme and deadly interstitial lung illness (ILD)/pneumonitis.

RYBREVANT ^® with LAZCLUZE™

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of sufferers handled with RYBREVANT ^® together with LAZCLUZE™, together with Grade 3 in 1.0% and Grade 4 in 0.2% of sufferers. There was one deadly case (0.2%) of ILD/pneumonitis and a couple of.9% of sufferers completely discontinued RYBREVANT ^® and LAZCLUZE™ on account of ILD/pneumonitis.

RYBREVANT ^® with Carboplatin and Pemetrexed

In PAPILLON, Grade 3 ILD/pneumonitis occurred in 2.6% of sufferers handled with RYBREVANT ^® together with carboplatin and pemetrexed, all sufferers required everlasting discontinuation.

RYBREVANT ^® as a Single Agent

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of sufferers handled with RYBREVANT ^®, with 0.7% of sufferers experiencing Grade 3 ILD/pneumonitis. Three sufferers (1%) discontinued RYBREVANT ^® on account of ILD/pneumonitis.

Monitor sufferers for brand new or worsening signs indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). For sufferers receiving RYBREVANT ^® together with LAZCLUZE™, instantly withhold each medication in sufferers with suspected ILD/pneumonitis and completely discontinue if ILD/pneumonitis is confirmed. For sufferers receiving RYBREVANT ^® as a single agent or together with carboplatin and pemetrexed, instantly withhold RYBREVANT ^® in sufferers with suspected ILD/pneumonitis and completely discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Occasions with Concomitant Use of RYBREVANT ^® and LAZCLUZE™

RYBREVANT ^® together with LAZCLUZE™ could cause critical and deadly venous thromboembolic (VTEs) occasions, together with deep vein thrombosis and pulmonary embolism. Nearly all of these occasions occurred in the course of the first 4 months of remedy.

In MARIPOSA, VTEs occurred in 36% of sufferers receiving RYBREVANT ^® together with LAZCLUZE™, together with Grade 3 in 10% and Grade 4 in 0.5% of sufferers. On-study VTEs occurred in 1.2% of sufferers (n=5) whereas receiving anticoagulation remedy. There have been two deadly circumstances of VTE (0.5%), 9% of sufferers had VTE resulting in dose interruptions of RYBREVANT ^®, and seven% of sufferers had VTE resulting in dose interruptions of LAZCLUZE™; 1% of sufferers had VTE resulting in dose reductions of RYBREVANT ^®, and 0.5% of sufferers had VTE resulting in dose reductions of LAZCLUZE™; 3.1% of sufferers had VTE resulting in everlasting discontinuation of RYBREVANT ^®, and 1.9% of sufferers had VTE resulting in everlasting discontinuation of LAZCLUZE™. The median time to onset of VTEs was 84 days (vary: 6 to 777).

Administer prophylactic anticoagulation for the primary 4 months of therapy. The usage of Vitamin Ok antagonists will not be advisable. Monitor for indicators and signs of VTE occasions and deal with as medically applicable.

Withhold RYBREVANT ^® and LAZCLUZE™ based mostly on severity. As soon as anticoagulant therapy has been initiated, resume RYBREVANT ^® and LAZCLUZE™ on the identical dose stage on the discretion of the healthcare supplier. Within the occasion of VTE recurrence regardless of therapeutic anticoagulation, completely discontinue RYBREVANT ^® and proceed therapy with LAZCLUZE™ on the identical dose stage on the discretion of the healthcare supplier.

Dermatologic Antagonistic Reactions

RYBREVANT ^® could cause extreme rash together with poisonous epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry pores and skin.

RYBREVANT ^® with LAZCLUZE™

In MARIPOSA, rash occurred in 86% of sufferers handled with RYBREVANT ^® together with LAZCLUZE™, together with Grade 3 in 26% of sufferers. The median time to onset of rash was 14 days (vary: 1 to 556 days). Rash resulting in dose interruptions occurred in 37% of sufferers for RYBREVANT ^® and 30% for LAZCLUZE™, rash resulting in dose reductions occurred in 23% of sufferers for RYBREVANT ^® and 19% for LAZCLUZE™, and rash resulting in everlasting discontinuation occurred in 5% of sufferers for RYBREVANT ^® and 1.7% for LAZCLUZE™.

RYBREVANT ^® with Carboplatin and Pemetrexed

In PAPILLON, rash occurred in 89% of sufferers handled with RYBREVANT ^® together with carboplatin and pemetrexed, together with Grade 3 (19%) antagonistic reactions. Rash resulting in dose reductions occurred in 19% of sufferers, and a couple of% completely discontinued RYBREVANT ^® and 1.3% discontinued pemetrexed.

RYBREVANT ^® as a Single Agent

In CHRYSALIS, rash occurred in 74% of sufferers handled with RYBREVANT ^® as a single agent, together with Grade 3 rash in 3.3% of sufferers. The median time to onset of rash was 14 days (vary: 1 to 276 days). Rash resulting in dose discount occurred in 5% of sufferers, and RYBREVANT ^® was completely discontinued on account of rash in 0.7% of sufferers.

Poisonous epidermal necrolysis occurred in a single affected person (0.3%) handled with RYBREVANT ^® as a single agent.

Instruct sufferers to restrict solar publicity throughout and for two months after therapy with RYBREVANT ^® or LAZCLUZE™ together with RYBREVANT ^®. Advise sufferers to put on protecting clothes and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is advisable for dry pores and skin.

When initiating RYBREVANT ^® therapy with or with out LAZCLUZE™, administer alcohol-free emollient cream to cut back the danger of dermatologic antagonistic reactions. Contemplate prophylactic measures (e.g. use of oral antibiotics) to cut back the danger of dermatologic reactions. If pores and skin reactions develop, begin topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and think about dermatologic session. Promptly refer sufferers presenting with extreme rash, atypical look or distribution, or lack of enchancment inside 2 weeks to a dermatologist. For sufferers receiving RYBREVANT ^® together with LAZCLUZE™, withhold, dose cut back or completely discontinue each medication based mostly on severity. For sufferers receiving RYBREVANT ^® as a single agent or together with carboplatin and pemetrexed, withhold, dose cut back or completely discontinue RYBREVANT ^® based mostly on severity.

Ocular Toxicity

RYBREVANT ^® could cause ocular toxicity together with keratitis, blepharitis, dry eye signs, conjunctival redness, blurred imaginative and prescient, visible impairment, ocular itching, eye pruritus, and uveitis.

RYBREVANT ^® with LAZCLUZE™

In MARIPOSA, ocular toxicity occurred in 16% of sufferers handled with RYBREVANT ^® together with LAZCLUZE™, together with Grade 3 or 4 ocular toxicity in 0.7% of sufferers. Withhold, cut back the dose, or completely discontinue RYBREVANT ^® and proceed LAZCLUZE™ based mostly on severity.

RYBREVANT ^® with Carboplatin and Pemetrexed

In PAPILLON, ocular toxicity together with blepharitis, dry eye, conjunctival redness, blurred imaginative and prescient, and eye pruritus occurred in 9%. All occasions had been Grade 1-2.

RYBREVANT ^® as a Single Agent

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of sufferers handled with RYBREVANT ^®. All occasions had been Grade 1-2.

Promptly refer sufferers with new or worsening eye signs to an ophthalmologist. Withhold, dose cut back or completely discontinue RYBREVANT ^® based mostly on severity.

Embryo-Fetal Toxicity

Based mostly on its mechanism of motion and findings from animal fashions, RYBREVANT ^® and LAZCLUZE™ could cause fetal hurt when administered to a pregnant lady. Advise females of reproductive potential of the potential danger to the fetus.

Advise feminine sufferers of reproductive potential to make use of efficient contraception throughout therapy and for 3 months after the final dose of RYBREVANT ^®.

Advise females of reproductive potential to make use of efficient contraception throughout therapy with LAZCLUZE™ and for 3 weeks after the final dose. Advise male sufferers with feminine companions of reproductive potential to make use of efficient contraception throughout therapy with LAZCLUZE™ and for 3 weeks after the final dose.

Antagonistic Reactions

RYBREVANT ^® with LAZCLUZE™

For the 421 sufferers within the MARIPOSA scientific trial who obtained RYBREVANT ^® together with LAZCLUZE™, the commonest antagonistic reactions ( ‰¥20%) had been rash (86%), nail toxicity (71%), infusion-related reactions (RYBREVANT ^®, 63%), musculoskeletal ache (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry pores and skin (25%), decreased urge for food (24%), pruritus (24%), nausea (21%), and ocular toxicity (16%). The commonest Grade 3 or 4 laboratory abnormalities ( ‰¥2%) had been decreased albumin (8%), decreased sodium (7%), elevated ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), elevated AST (3.8%), elevated GGT (2.6%), and elevated magnesium (2.6%).

Critical antagonistic reactions occurred in 49% of sufferers who obtained RYBREVANT ^® together with LAZCLUZE™. Critical antagonistic reactions occurring in ‰¥2% of sufferers included VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% every), COVID-19 (2.4%), and pleural effusion and infusion-related response (RYBREVANT ^®) (2.1% every). Deadly antagonistic reactions occurred in 7% of sufferers who obtained RYBREVANT ^® together with LAZCLUZE™ on account of loss of life not in any other case specified (1.2%); sepsis and respiratory failure (1% every); pneumonia, myocardial infarction, and sudden loss of life (0.7% every); cerebral infarction, pulmonary embolism (PE), and COVID-19 an infection (0.5% every); and ILD/pneumonitis, acute respiratory misery syndrome (ARDS), and cardiopulmonary arrest (0.2% every).

RYBREVANT ^® with Carboplatin and Pemetrexed

For the 151 sufferers within the PAPILLON scientific trial who obtained RYBREVANT ^® together with carboplatin and pemetrexed, the commonest antagonistic reactions ( ‰¥20%) had been rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related response (42%), fatigue (42%), edema (40%), constipation (40%), decreased urge for food (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The commonest Grade 3 to 4 laboratory abnormalities ( ‰¥2%) had been decreased albumin (7%), elevated alanine aminotransferase (4%), elevated gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and reduces in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

Critical antagonistic reactions occurred in 37% of sufferers who obtained RYBREVANT ^® together with carboplatin and pemetrexed. Critical antagonistic reactions in ‰¥2% of sufferers included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Deadly antagonistic reactions occurred in 7 sufferers (4.6%) on account of pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and loss of life not in any other case specified.

RYBREVANT ^® as a Single Agent

For the 129 sufferers within the CHRYSALIS scientific trial who obtained RYBREVANT ^® as a single agent, the commonest antagonistic reactions ( ‰¥20%) had been rash (84%), IRR (64%), paronychia (50%), musculoskeletal ache (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The commonest Grade 3 to 4 laboratory abnormalities ( ‰¥2%) had been decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), elevated alkaline phosphatase (4.8%), elevated glucose (4%), elevated gamma-glutamyl transferase (4%), and decreased sodium (4%).

Critical antagonistic reactions occurred in 30% of sufferers who obtained RYBREVANT ^®. Critical antagonistic reactions in ‰¥2% of sufferers included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal ache, pneumonia, and muscular weak spot. Deadly antagonistic reactions occurred in 2 sufferers (1.5%) on account of pneumonia and 1 affected person (0.8%) on account of sudden loss of life.

LAZCLUZE™ Drug Interactions

Keep away from concomitant use of LAZCLUZE™ with robust and average CYP3A4 inducers. Contemplate an alternate concomitant treatment with no potential to induce CYP3A4.

Monitor for antagonistic reactions related to a CYP3A4 or BCRP substrate the place minimal focus modifications might result in critical antagonistic reactions, as advisable within the authorised product labeling for the CYP3A4 or BCRP substrate.

Please learn full Prescribing Info for RYBREVANT ^®.

Please learn full Prescribing Info for LAZCLUZE™.

About Johnson & Johnson

At Johnson & Johnson, we imagine well being is the whole lot. Our power in healthcare innovation empowers us to construct a world the place complicated ailments are prevented, handled, and cured, the place remedies are smarter and fewer invasive, and options are private. By means of our experience in Modern Medication and MedTech, we’re uniquely positioned to innovate throughout the complete spectrum of healthcare options at present to ship the breakthroughs of tomorrow, and profoundly influence well being for humanity. Study extra at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Observe us at @JanssenUS and @JNJInnovMed. Janssen Analysis & Growth, LLC, and Janssen Biotech, Inc. are Johnson & Johnson corporations.

Cautions Regarding Ahead-Trying Statements

This press launch comprises “forward-looking statements” as outlined within the Non-public Securities Litigation Reform Act of 1995 concerning product growth and the potential advantages and therapy influence of RYBREVANT ^® (amivantamab-vmjw) and LAZCLUZE™ (lazertinib). The reader is cautioned to not depend on these forward-looking statements. These statements are based mostly on present expectations of future occasions. If underlying assumptions show inaccurate or identified or unknown dangers or uncertainties materialize, precise outcomes might differ materially from the expectations and projections Janssen Analysis & Growth, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Dangers and uncertainties embody, however usually are not restricted to: challenges and uncertainties inherent in product analysis and growth, together with the uncertainty of scientific success and of acquiring regulatory approvals; uncertainty of economic success; manufacturing difficulties and delays; competitors, together with technological advances, new merchandise and patents attained by rivals; challenges to patents; product efficacy or security issues leading to product recollects or regulatory motion; modifications in habits and spending patterns of purchasers of well being care services; modifications to relevant legal guidelines and rules, together with international well being care reforms; and tendencies towards well being care value containment. An additional record and descriptions of those dangers, uncertainties and different elements may be present in Johnson & Johnson’s Annual Report on Kind 10-Ok for the fiscal yr ended December 31, 2023, together with within the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Studies on Kind 10-Q and different filings with the Securities and Trade Fee. Copies of those filings can be found on-line at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Analysis & Growth, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to replace any forward-looking assertion because of new data or future occasions or developments.

Dr. Shirish M. Gadgeel has supplied consulting, advisory, and talking companies to Johnson & Johnson; he has not been paid for any media work.

See the NCCN Pointers for detailed suggestions, together with different therapy choices.

^¡The NCCN Pointers for NSCLC present suggestions for sure particular person biomarkers that ought to be examined and suggest testing methods however don’t endorse any particular commercially accessible biomarker assays or business laboratories.

^§The NCCN Content material doesn’t represent medical recommendation and shouldn’t be used instead of searching for skilled medical recommendation, analysis or therapy by licensed practitioners. NCCN makes no warranties of any type in anyway concerning their content material, use or software and disclaims any duty for his or her software or use in any means.