RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) combination demonstrates 77% overall response rate in first-line treatment of patients with advanced head and neck cancer

Responses remained ongoing in 65% of responders in the 22-patient subgroup at median follow-up of 10.6 months.

Rhea-AI Summary

Johnson & Johnson (JNJ) reported a 77% response rate for its investigational RYBREVANT FASPRO combination in first-line advanced head and neck cancer.

Phase 1b/2 OrigAMI-4 Cohort 5 tested subcutaneous amivantamab with pembrolizumab and up to six carboplatin cycles. Among 22 patients without HPV-associated oropharyngeal cancer, confirmed tumor responses occurred in 77%, including complete responses in 14%; 65% of responses remained ongoing at median follow-up of 10.6 months. One-year overall survival was 77%. The seven patients with HPV-associated oropharyngeal cancer had a 29% response rate.

Common adverse events included anemia (73%), hypoalbuminemia (63%), thrombocytopenia (63%) and stomatitis (57%). The first-line Phase 3 OrigAMI-5 study is ongoing. A separate application for later-line head and neck cancer is under FDA Priority Review.

7 points · 0 major

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Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

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0 major · 5 points

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Positive

• Moderate pointLater-line head and neck cancer application has FDA Priority Review status.
• Minor pointConfirmed response rate reached 77% among 22 patients without HPV-associated oropharyngeal cancer; complete responses reached 14%.
• Minor pointResponses remained ongoing in 65% of responders at median follow-up of 10.6 months in that subgroup.
• Minor pointMedian time to response was 9.4 weeks in patients without HPV-associated oropharyngeal cancer.
• Minor pointOne-year overall survival was 77% in that subgroup; median overall survival was not reached.

2 minor points

• Minor pointHPV-associated oropharyngeal cancer subgroup achieved a 29% response rate among seven patients.
• Minor pointFirst-line development continues in the ongoing Phase 3 OrigAMI-5 study.

Negative

• Minor pointAnemia occurred in 73% of patients receiving the three-drug regimen.
• Minor pointHypoalbuminemia, or low blood albumin, occurred in 63% of patients.
• Minor pointThrombocytopenia, or low platelet counts, occurred in 63% of patients.
• Minor pointStomatitis, or mouth inflammation, occurred in 57% of patients.
• Minor pointAdministration-related reactions occurred in 13% of patients, with no Grade 3 or higher events reported.

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• Responses were deep and durable, with 65% ongoing at clinical cutoff
• Results support continued evaluation of the investigational RYBREVANT FASPRO regimen in the ongoing first-line Phase 3 study
• Data highlight the role of dual-targeting EGFR and MET, key drivers of tumor growth and resistance seen in 80 to 90 percent of HNSCC

NEW BRUNSWICK, N.J., Oct. 25, 2026 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced new results from Cohort 5 of the Phase 1b/2 OrigAMI-4 study showing deep and durable responses with first-line subcutaneous amivantamab and hyaluronidase-lpuj plus a PD-1 inhibitor and fixed-duration carboplatin chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).¹ These findings support the ongoing pivotal Phase 3 OrigAMI-5 study and further expand the clinical development program for subcutaneous amivantamab for patients with head and neck cancer.²

Among patients with HNSCC other than human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), results demonstrated a confirmed overall response rate (ORR) of 77 percent, including 14 percent achieving complete responses.¹ Tumor shrinkage was observed in all evaluable patients, and nearly two-thirds of responses remained ongoing at a median follow-up of 10.6 months.¹ These findings were presented as a rapid oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract #1539RO). An application for RYBREVANT FASPRO in later-line head and neck cancer is also under Priority Review with the U.S. Food and Drug Administration (FDA).

Unmet need remains in first-line head and neck cancer treatment

For people with recurrent or metastatic head and neck cancer, the first treatment decision comes at a critical point in an aggressive disease often associated with poor prognosis.³ While some patients benefit from the current standard of care, many experience disease progression while facing symptoms that can profoundly affect daily life, including the ability to eat, swallow and speak.^4,5 Nearly 60 percent of patients do not go on to receive subsequent treatment,⁶ underscoring the need to help more patients achieve meaningful tumor reduction and durable responses from the start.

Subcutaneous amivantamab is a bispecific antibody designed to dual-target epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) while also engaging the immune system.^7,8,9 Overexpression of EGFR and MET is seen in 80 to 90 percent of HNSCC tumors and has been implicated in tumor progression and treatment resistance.¹⁰ The approach has been well-validated in EGFR-mutated lung cancer where data suggest that targeting both pathways may disrupt disease biology and improve outcomes.^11,12

Expert and company perspectives on RYBREVANT FASPRO's role in advancing first-line treatment

"The first treatment a patient receives for recurrent or metastatic head and neck cancer can shape everything that follows," said Paul Swiecicki, M.D.,* associate professor of Hematology/Oncology at University of Michigan Rogel Cancer Center. "The responses seen with subcutaneous amivantamab give us reason to think differently about what may be possible from the start of treatment, especially as we see responses across the majority of patients with head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma, many of which are rapid, deep and persist over time."

"We've already seen what subcutaneous amivantamab may offer patients with head and neck cancer after their disease has progressed. Now, we see the potential impact of using this approach earlier in recurrent or metastatic disease," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "Our experience with RYBREVANT FASPRO in lung cancer has helped establish the potential of dual EGFR/MET targeting, and these results support continued evaluation of this approach in head and neck cancer."

RYBREVANT FASPRO demonstrates meaningful anti-tumor activity in first-line disease

Cohort 5 of the OrigAMI-4 study evaluated subcutaneous amivantamab in combination with pembrolizumab (PD-1 inhibitor) and up to six cycles of carboplatin in previously untreated patients with recurrent or metastatic HNSCC. Patients received treatment every three weeks following the initial treatment period, with an administration time of five minutes or less. The primary endpoint was ORR, as assessed by investigators using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Response rates were assessed separately in patients with HPV-associated OPSCC (n=7) and patients with all other forms of HNSCC (n=22), given known differences in how these patient populations respond to EGFR-targeted bispecifics.¹

Thirty patients received subcutaneous amivantamab in combination with pembrolizumab and carboplatin, and 29 were included in the efficacy analysis. One patient was deemed ineligible. Among the 22 patients with forms of HNSCC other than HPV-associated OPSCC, the confirmed ORR was 77 percent (95 percent confidence interval [CI], 55-92), including complete responses in 14 percent and partial responses in 64 percent. Responses occurred at a median of 9.4 weeks, with 65 percent ongoing at a median follow-up of 10.6 months. Four patients (18 percent) had stable disease and one (5 percent) had progressive disease. Median overall survival was not reached, and 77 percent of patients were alive at one year. The remaining seven patients had HPV-associated OPSCC, with an ORR of 29 percent (95 percent CI, 4-71).¹

The safety profile of subcutaneous amivantamab in combination with pembrolizumab and carboplatin was consistent with the individual agents. The most common adverse events were anemia (73 percent), hypoalbuminemia (63 percent), thrombocytopenia (63 percent) and stomatitis (57 percent). Administration-related reactions associated with subcutaneous amivantamab occurred in 13 percent of patients, with no Grade 3 or higher events reported.¹

The Cohort 5 findings build on earlier first-line results from the OrigAMI-4 program, including Cohort 2 data evaluating subcutaneous amivantamab in combination with pembrolizumab recently published in Clinical Cancer Research.¹³

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 six cohorts exploring RYBREVANT FASPRO across different treatment settings and regimens.¹⁴

Cohort 5 of the OrigAMI-4 study evaluated RYBREVANT FASPRO, administered every three weeks, in combination with pembrolizumab and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma receiving first-line treatment whose tumors tested positive for programmed death-ligand 1 (PD-L1), with a combined positive score (CPS) of 1 or greater. The primary endpoint was ORR, as assessed by investigators using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).^† 14

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.¹⁵ It represents approximately 4.5 percent of all cancers worldwide and is the seventh most common cancer globally.¹⁵ Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).¹⁵ 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.^15,16 Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.^17,18

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 for these EGFR-mutated NSCLC populations and may be used as monotherapy or in combination with LAZCLUZE^® (lazertinib) or chemotherapy, depending on the specific mutation and treatment setting. For eligible patients, RYBREVANT FASPRO offers a once-monthly dosing option following initial weekly dosing. RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology.

RYBREVANT FASPRO is approved in the U.S. for the same indications as intravenous RYBREVANT (amivantamab-vmjw) 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 National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®)^‡ 19 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 https://www.jnj.com/.  

RYBREVANT FASPRO and RYBREVANT^® IMPORTANT SAFETY INFORMATION^20, 21

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

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.

cp-491009v2

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT^®-based regimens. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

*Paul Swiecicki, M.D., has served as a consultant to Johnson & Johnson; he 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.

^‡ 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.

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1 Swiecicki, PL, et al. Amivantamab + pembrolizumab + carboplatin in first-line recurrent/metastatic head & neck squamous cell cancer (1L R/M HNSCC) Results from the phase 1b/2 OrigAMI-4 study. Presented at: 2026 European Society for Medical Oncology (ESMO) Congress; October 25, 2026; Madrid, Spain. 2 ClinicalTrials.gov. A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer (OrigAMI-5). https://clinicaltrials.gov/study/NCT07276399?term=origami-5&viewType=Card&rank=1. Accessed October 2026. 3 Park JC, Ye GH, Merkin R, et al. Outcomes for recurrent or metastatic head and neck cancer by HPV status: a systematic review and meta-analysis. Oncologist. 2025;30(4):oyaf043. doi:10.1093/oncolo/oyaf043 4 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  5 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 6 Lee DY, Pan A, Yaskolko M, et al. Real world treatment patterns for recurrent and metastatic head and neck cancer in the post-KEYNOTE 048 era. Front Oncol. 2025;15:1577509. doi: 10.3389/fonc.2025.1577509 7 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 8 Fasano M, Della Corte CM, Viscardi G et al. Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy. Ther Adv Med Oncol. 2021;13:1758835920949418. 9 Cho BC, Simi A, Sabari J, et al. 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;24:89–97. 10 Kalyankrishna S, Grandis JR. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006;24(17):2666-2672. 11 Cho BC, Lu S, Felip E, et al. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. doi:10.1056/NEJMoa2403614 12 Yang JCH, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001 13 Kao H-F, Harrington K, Bhatia A, et al. Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: Results from the phase 1b/2 OrigAMI-4 study. Clinical Cancer Research. Published online September 15, 2026. doi:10.1158/1078-0432.CCR-26-1372 14 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 October 2026. 15 Barsouk A, Aluru JS, Rawla P, et al. 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 16 Ghiani L, Chiocca S. High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. Int J Mol Sci. 2022;23(7):3483. https://doi.org/10.3390/ijms23073483 17 Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252 18 Wise-Draper TM, Bahig H, Tonneau M, et al. 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 19 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2026 © National Comprehensive Cancer Network, Inc. All rights reserved. Accessed October 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. 20 RYBREVANT FASPRO [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 21 RYBREVANT [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

 

Media contact: Oncology Media Relations oncology_media_relations@its.jnj.com	Investor contact: Jess Margevich investor-relations@its.jnj.com
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SOURCE Johnson & Johnson

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Johnson & Johnson's RYBREVANT FASPRO head and neck cancer trial show?

The combination achieved a confirmed 77% response rate among 22 patients without HPV-associated oropharyngeal cancer, including complete responses in 14%. The 95% confidence interval was 55–92%. Among seven patients with HPV-associated oropharyngeal cancer, the response rate was 29%, with a 95% confidence interval of 4–71%.

Who was eligible for JNJ's OrigAMI-4 Cohort 5 head and neck cancer study?

Cohort 5 enrolled previously untreated patients with recurrent or metastatic head and neck squamous cell carcinoma whose tumors were PD-L1 positive, with a combined positive score of 1 or greater. Thirty patients received treatment; 29 were included in the efficacy analysis, and one was deemed ineligible.

How were responses assessed in JNJ's OrigAMI-4 Cohort 5 trial?

Investigators assessed the primary endpoint, overall response rate, using RECIST version 1.1, a standardized method for measuring tumor response. OrigAMI-4 is an open-label Phase 1b/2 study, and response rates were assessed separately for patients with HPV-associated oropharyngeal cancer and those with other forms of head and neck squamous cell carcinoma.