RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) pivotal data show strong and durable responses in advanced head and neck cancer where options remain limited

A supplemental Biologics License Application (sBLA) seeking approval for subcutaneous amivantamab in head and neck cancer has been submitted to the U.S. Food and Drug Administration (FDA), following Breakthrough Therapy Designation.

High unmet need remains in advanced head and neck cancer

Head and neck squamous cell carcinoma is an aggressive disease that can significantly affect quality of life, with symptoms such as pain and difficulty swallowing that can make it hard to eat, speak and maintain proper nutrition.^3,4 Certain forms of head and neck cancer, including tumors of the mouth, voice box and parts of the throat, are among the most difficult to treat, and are associated with poorer outcomes and persistent unmet need.⁵ Across head and neck cancers, up to half of patients will experience recurrence or metastatic disease, even when treated at an early stage.³ Once the disease becomes recurrent or metastatic, five-year survival is approximately 15 percent.⁶ For patients who receive additional treatment, current options provide limited benefit with response rates rarely exceeding 24 percent, and few patients achieve a complete response.^7,8

Dual-targeting mechanism helps address tumor growth and resistance

Subcutaneous amivantamab is designed to dual target both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), two pathways associated with tumor growth and resistance, while engaging the immune system.⁹

"Patients with recurrent or metastatic head and neck cancer who have already been treated with immunotherapy and chemotherapy face very poor outcomes," said Barbara Burtness, M.D.,* medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut. "The high response seen with subcutaneous amivantamab on its own, including more than one-third of responders achieving complete responses, and the durability of those responses, suggests it has the potential to meaningfully improve expectations for these patients."

Detailed OrigAMI-4 study results

Cohort 1 of the OrigAMI-4 study evaluated subcutaneous amivantamab monotherapy in 102 patients with recurrent or metastatic head and neck cancer who had previously received immunotherapy and platinum-based chemotherapy, excluding patients with human papillomavirus (HPV)-positive oropharyngeal cancer. Patients received treatment every three weeks following an initial loading dose. The primary endpoint was overall response rate, as assessed by local investigators per protocol. Responses were confirmed via blinded independent central review (BICR).¹

Based on BICR, confirmed overall response rate was 42 percent (95 percent confidence interval [CI], 32-52), including complete responses in more than one-third of responders (15 percent) and a 27 percent partial response rate. Clinical benefit rate was 63 percent (95 percent CI, 53-72), and median time to first response was 6.6 weeks (range, 5.6-36.9). At the time of analysis (median follow-up of 11.8 months), median duration of response had not yet been reached among confirmed responders, demonstrating notable durability. Median progression-free survival and overall survival were 6.8 months and 12.5 months, respectively.¹

The safety profile of subcutaneous amivantamab monotherapy was consistent with prior reports, with no new safety signals identified. Most treatment-related adverse events were Grade 1 or 2 (mild to moderate) and associated with EGFR or MET inhibition. The most common on-target adverse events included hypoalbuminemia (50 percent), rash (37 percent), paronychia (34 percent) and dermatitis acneiform (34 percent). Administration-related reactions occurred in 15 percent of patients, with no Grade 3 or higher events reported. Treatment-related discontinuations remained low at eight percent.¹

"Progress has been limited for patients with recurrent and metastatic head and neck cancer, highlighting the need for differentiated approaches that can address the disease more comprehensively," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "Subcutaneous amivantamab is the only therapy of its kind being studied in this disease, targeting both EGFR and MET while engaging the immune system. The encouraging responses we're seeing in OrigAMI-4, along with a well-established and manageable safety profile, underscore the potential of this approach and move us closer to delivering a fast, convenient treatment option."

Ongoing study of RYBREVANT FASPRO™ in head and neck cancer

A trial-in-progress update from the Phase 3 OrigAMI-5 study (NCT07276399) was also shared at ASCO 2026 (Abstract #583a). The study is evaluating subcutaneous amivantamab in combination with carboplatin and pembrolizumab as a first-line treatment for patients with recurrent or metastatic head and neck cancer, with the goal of improving outcomes in the first-line setting.¹⁰

RYBREVANT FASPRO™ is already approved in more than 40 countries, including the United States, Europe, Japan, and other markets, as a subcutaneous treatment for patients with EGFR-mutated non-small cell lung cancer.¹¹

About the OrigAMI-4 Study

OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study evaluating RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes five cohorts exploring RYBREVANT FASPRO™ across different treatment settings and regimens.

Cohort 1 evaluated RYBREVANT FASPRO™ as monotherapy in patients with R/M HNSCC who had received prior platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Patients with HPV-positive oropharyngeal squamous cell carcinoma were excluded, as well as those with prior anti-EGFR therapy.

RYBREVANT FASPRO™ was administered on a weekly schedule during the initial treatment period followed by dosing every three weeks (Q3W), with weight-based dosing adjustments. The primary endpoint across cohorts is overall response rate (ORR), as assessed by investigators, using RECIST v1.1.^†12

About Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer, a group of cancers that arise in the mouth, throat, voice box, sinuses, nasal cavity, and salivary glands.¹³ It represents approximately 4.5 percent of all cancers worldwide and is the seventh most common cancer globally.¹³ Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).¹³ Approximately 80 percent of recurrent or metastatic HNSCC are not driven by HPV, and are typically associated with poorer prognosis and reduced response to treatment.^{13, 14} Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.^15,16

About RYBREVANT FASPRO™ and 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. RYBREVANT^® 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^®)^§17 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 FASPRO™ and RYBREVANT^® is Janssen Biotech, Inc. For more information, 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 FOR RYBREVANT FASPRO™ AND RYBREVANT^® 10,18

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 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^®.

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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.

*Barbara Burtness, M.D. has served as a consultant to Johnson & Johnson; she has not been paid for any media work. 

^† RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger.

^‡ 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.

¹ Burtness B, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy. Pivotal results from the phase 1b/2 OrigAMI-4 study. Presented at: The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31, 2026; Chicago, Illinois.

² Burtness B, et al. Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. Epub May 31, 2026. doi:10.1200/JCO-26-01042.

³ Zebralla V, Wichmann G, Pirlich M, et al. Dysphagia, voice problems, and pain in head and neck cancer patients. Eur Arch Otorhinolaryngol. 2021;278(10):3985-3994. doi:10.1007/s00405-020-06584-6

⁴ Nissi L, et al. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin Transl Radiat Oncol. 2021;27:139-146. doi:10.1016/j.ctro.2021.01.013

⁵ Dunn LA, Ho AL, Pfister DG. Head and neck cancer: a review. JAMA. 2026;335(6):531-541. doi:10.1001/jama.2025.21733

⁶ Soulieres D, et al. LBA48 BURAN: A phase III study of buparlisib (BUP) plus paclitaxel (PAC) in patients with PD-1(PD-L1)-pretreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Ann Oncol. 2025;36:S1707.

⁷ Fayette J, et al. INTERLINK-1: A Phase III, randomized, placebo-controlled study of monalizumab plus cetuximab in recurrent/metastatic head and neck squamous cell carcinoma. Clin Cancer Res. 2025;31(13):2617-2627. doi:10.1158/1078-0432.CCR-25-0073

⁸ Große-Thie C, Maletzki C, Junghanss C, Schmidt K. Long-term survivor of metastatic squamous-cell head and neck carcinoma with occult primary after cetuximab-based chemotherapy: A case report. World J Clin Cases. 2021;9(24):7092-7098. doi:10.12998/wjcc.v9.i24.7092

⁹ Harrington KJ, Rosenberg AJ, Yang MH, et al. Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study. Oral Oncol. 2025;171:107791. doi:10.1016/j.oraloncology.2025.107791

¹⁰ Haddad R, et al. OrigAMI-5: A randomized, phase 3 study of amivantamab plus pembrolizumab and carboplatin vs standard of care pembrolizumab plus platinum and 5-fluorouracil as first-line treatment in recurrent/metastatic head and neck cancer. Presented at: The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30, 2026; Chicago, Illinois.

¹¹ RYBREVANT FASPRO™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

¹² ClinicalTrials.gov. A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4). https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1. Accessed May 2026.

¹³ Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023;11(2):42. Published 2023 Jun 13. doi:10.3390/medsci11020042

¹⁴ Ghiani L, Chiocca S. High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. International Journal of Molecular Sciences. 2022;23(7):3483. https://doi.org/10.3390/ijms23073483

¹⁵ Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. New England Journal of Medicine. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252

¹⁶ Wise-Draper TM, Bahig H, Tonneau M, Karivedu V, Burtness B. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_350442

¹⁷ 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.

¹⁸ RYBREVANT^® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

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