A subcutaneous option reshaping EGFR-mutated NSCLC care

In cancer care, few things are more precious than time. For patients with advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth-factor receptor (EGFR) mutations including exon 19 deletion, exon 21 L858R substitution, or exon 20 insertion, a subcutaneous (SC) treatment called RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) offers a more convenient way to receive RYBREVANT^® (amivantamab-vmjw)-based therapy, with the possibility of living longer, which could mean spending more time with the people who matter most.

RYBREVANT FASPRO™ is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients.

WARNINGS AND PRECAUTIONS for RYBREVANT^® and RYBREVANT FASPRO™ include: infusion-related reactions (IRRs) (RYBREVANT^®), hypersensitivity & administration-related reactions (ARRs) (RYBREVANT FASPRO™), interstitial lung disease/pneumonitis, venous thromboembolism, dermatologic adverse reactions, hepatotoxicity, ocular toxicity and embryo-fetal toxicity. See additional safety information below.

A First-of-Its-Kind Approval

The approval of RYBREVANT FASPRO™ by the U.S. Food and Drug Administration marks a turning point in the lung cancer treatment landscape, offering an SC treatment approved for all current RYBREVANT^® indications, with flexible dosing that allows for monthly* or every-two-week administration depending on the regimen. This SC option offers consistent pharmacokinetics and safety results compared to intravenous (IV) RYBREVANT^®, while reducing administration-related reactions (ARR) (13% vs 66%), and decreasing the administration time from five hours to approximately five minutes per injection(s).**^1,2

*Following weekly doses from weeks 1 to 4. For patients currently following a Q2W dosing regimen, switch to subcutaneous and/or Q4W dosing at their next scheduled dose after initial weekly dosing has been completed (on or after week 5).

**This reflects administration time only; actual clinic time may vary.

This advancement builds on decades of progress in EGFR-targeted research. Early discoveries of EGFR mutations and successive generations of tyrosine kinase inhibitors (TKIs) reshaped the way NSCLC is treated, moving beyond conventional chemotherapy to more precise, targeted approaches.^3,4 Within this wave of innovation, therapies such as RYBREVANT^® were developed to expand treatment options for patients with specific EGFR mutations not effectively targeted by existing therapies.⁴ RYBREVANT^® is a bispecific antibody that works through a unique multi-targeted mechanism of action that blocks and degrades EGFR and MET and activates the immune system. When paired with LAZCLUZE^® (lazertinib), a third-generation EGFR TKI that blocks EGFR intracellularly, this combination provides complementary extra- and intracellular antitumor activity and central nervous system penetration.^5-8 The combination became the first chemotherapy-free combination regimen studied in a Phase 3 clinical trial to show that patients with EGFR-mutated NSCLC receiving first-line treatment could live longer than those treated with prior standards of care.^6,9

Delivering on Innovation: The Research that Led to Subcutaneous Delivery

The efficacy of RYBREVANT FASPRO™ is established in well-controlled trials with IV RYBREVANT^® including the Phase 3 PALOMA-3 trial which compared subcutaneous RYBREVANT FASPRO™ with LAZCLUZE^® (n=206) to the IV regimen of RYBREVANT^® plus LAZCLUZE^® (n=212). The study met both co-primary pharmacokinetics endpoints which demonstrated comparable systemic drug exposure for the subcutaneous and IV formulations. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), duration of response (DoR), and safety. Secondary efficacy results showed similar ORR for both subcutaneous and IV formulations. Secondary analyses were not powered for statistical significance.¹

• Pharmacokinetics: SC delivery achieved drug exposure levels similar to IV RYBREVANT^® (Cycle 2 Day 1 C_trough 365 vs 314 µg/mL; GMR 1.15; [90% CI, 1.04 to 1.26]; Cycle 2 AUC_D1-D15 142,236 vs 135,552 µg·h/mL; GMR 1.03; [90% CI, 0.98-1.09]), meeting primary study goals.
• Reduced administration time: SC delivery took a median of 4.8 minutes compared with about five hours for the first IV dose. This reflects administration time only; actual clinic time may vary.
• Fewer key adverse events: The SC regimen showed a five-fold reduction in ARRs (13% vs 66%), and lower rates of blood clots (11% vs 18%).
• Patient satisfaction: More than 80% of patients reported that the SC option was more convenient, with 85% rating it convenient at both the start and end of treatment compared with 52% (start of treatment) and 35% (end of treatment) for IV.^10,11

The safety profile of RYBREVANT FASPRO™ was generally consistent with the IV formulation when used in combination with LAZCLUZE^®, with lower rates of ARRs (13% vs 66%) and venous thromboembolism (11% vs 18%). ARRs were not only less frequent but also milder, with fewer grade 3 or 4 events observed (0.5% vs 3.8%). The most common adverse reactions, affecting at least 20% of patients, included rash (80% vs 78%), nail toxicity (58% vs 56%), and musculoskeletal pain (50% vs 35%).¹

Building on Survival Gains

These findings are part of the larger story of RYBREVANT^®-based regimens and their role in advancing patient care. In the Phase 3 MARIPOSA trial, published in The New England Journal of Medicine, the combination of IV RYBREVANT^® and LAZCLUZE^® delivered unmatched overall survival compared with osimertinib monotherapy in newly diagnosed patients with EGFR exon 19 deletion and exon 21 L858R substitution mutations. Patients receiving the combination experienced a statistically significant and clinically meaningful improvement in overall survival, with median overall survival projected to exceed four years.^† MARIPOSA showed⁶:

• Longer PFS: Patients lived approximately seven months longer without disease progression on the combination (median PFS 23.7 vs 16.6 months with osimertinib; HR 0.70; 95% CI, 0.58-0.85; P=0.0002), lowering the risk of progression or death by 30%.
• Improved OS: Follow-up data confirmed a statistically significant survival benefit (HR 0.75; 95% CI, 0.61-0.92; P=0.0048). The median overall survival for the combination has not yet been reached (95% CI, 42.9-not estimable) but is projected to exceed four years–more than a year beyond what was possible with osimertinib.
• Safety outcomes: Most adverse reactions with IV RYBREVANT^® plus LAZCLUZE^® were Grade 1 or 2. Serious adverse reactions occurred in 49% of patients treated with the combination compared with 33% of patients treated with osimertinib. Serious adverse reactions reported in more than 2% of patients included venous thromboembolism (11%), pneumonia (4%), rash (2.9%), ILD/pneumonitis (2.9%), COVID-19 (2.4%), pleural effusion (2.1%), and infusion-related reactions (2.1%).

† Projected median OS is based on modeling using observed HR and median OS in the osimertinib group, assuming exponential distribution of OS in both arms. The baseline factors were: mutation type, race, brain metastases, age, sex, ECOG PS and weight. This is a conservative estimate; final results may vary.

See additional safety information below.

A New Experience of Care

For clinicians and patients, this milestone is as much about experience as outcomes. Joshua Bauml, M.D., Vice President and Lung/Head & Neck Cancer Disease Area Leader at Johnson & Johnson, noted that the goal was to improve outcomes and help make treatment easier to integrate into daily life. “RYBREVANT FASPRO™ delivers consistent results similar to what we see with IV treatment, helping patients live longer, while also preserving chemotherapy for later and doing it in a way that’s quicker for patients, easier for them to manage, and less taxing on healthcare teams,” he said.

The Next Chapter in NSCLC Treatment

With approvals now in both the US and Europe, RYBREVANT FASPRO™ is set to improve care for people with EGFR-mutated advanced NSCLC. As part of a treatment approach that has raised survival expectations, the SC regimen offers a simpler experience and a future where life-extending therapies don’t have to mean long administration times in a clinic or infusion center. Actual time on site can vary, but the shift to SC helps treatment fit more easily into the lives of the patients who need it.

For more information on RYBREVANT FASPRO™, visit www.rybrevanthcp.com.

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 INFORMATION

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.

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. 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.

Please see full Prescribing Information for RYBREVANT FASPRO, RYBREVANT and LAZCLUZE.

cp-491009v2

References:

1. RYBREVANT FASPRO™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
2. Leighl N, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor–mutated non–small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605.
3. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497-1500. doi:10.1126/science.1099314
4. Zhou F, Guo H, Xia Y, et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer. Nat Rev Clin Oncol. 2005:22(2);95–116. https://doi.org/10.1038/s41571-024-00971-2
5. Cho BC, Simi A., Sabari J, Vijayaraghavan S, Moores S, Spira A. Amivantamab, an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) bispecific antibody, designed to enable multiple mechanisms of action and broad clinical applications. Clin Lung Cancer. 2023;24(2):89-97. doi.org/10.1016/j.cllc.2022.11.004
6. Yang, JC-H, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutant advanced NSCLC. N Engl J Med. 2025. Online ahead of print.
7. LAZCLUZE^® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
8. Yun J, Hong MH, Kim SY, et al. YH25448, an irreversible EGFR-TKI with potent intracranial activity in EGFR mutant non–small cell lung cancer. Clin Cancer Res. 2019;25(8):2575-2587.
9. Hayashi H, Besse B, Lee S-H, et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib vs osimertinib: updated analysis from MARIPOSA. [Abstract PT1.03.06]. Presented at: IASLC 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain.
10. George S, Bourlon MT, Overman MJ, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: A clinical, economic and patient perspective. Cancer Treatment Reviews. 2025;139(102974):1-13.
11. Aguiar-Ibáñez R, Fotheringham I, Mittal L, et al. Differences between intravenous and subcutaneous modes of administration in oncology from the patient, healthcare provider, and healthcare system perspectives: a systematic review. Adv Ther. 2024;41(12):4396-4417.

cp-540259v2