On October 19, 2025 Pfizer Inc. (NYSE: PFE) reported updated follow-up results from the single-arm Phase 2 PHAROS trial evaluating BRAFTOVI (encorafenib) + MEKTOVI (binimetinib) for the treatment of adults with metastatic non-small cell lung cancer (mNSCLC) with a BRAF V600E mutation. In treatment-naïve patients, the median overall survival (OS) was 47.6 months (95% confidence interval [CI], 31.3, not estimable) after a median follow-up of 52.3 months. In previously treated patients, the median OS was 22.7 months (95% CI, 14.1, 32.6), after a median follow-up of 48.2 months. The four-year OS rates were 49% (95% CI, 35, 62) and 31% (95% CI, 16, 47) for treatment-naïve and previously treated patients, respectively. These data, from pre-specified secondary trial endpoints, will be presented today in an oral presentation (1849MO) at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany, and have been simultaneously published in the Journal of Clinical Oncology.

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"The PHAROS trial results set a new standard for NSCLC patients with the BRAF V600E mutation, with survival outcomes nearing four years—the longest survival we’ve seen in people with treatment-naïve metastatic NSCLC who harbor a BRAF V600E mutation," said Melissa Johnson, M.D., Director of Lung Cancer Research at Sarah Cannon Research Institute and PHAROS investigator. "These findings, which highlight the potential impact of encorafenib and binimetinib for newly diagnosed metastatic NSCLC patients with BRAF V600E, offer renewed optimism for their prognosis and treatment goals."

Lung cancer is the number one cause of cancer-related deaths around the world.1 NSCLC accounts for approximately 80-85% of lung cancers,2 with BRAF V600E mutations occurring in about 2% of patients with NSCLC.3 Prior to the development of targeted treatments, patients with BRAF V600E-mutant metastatic NSCLC had poor outcomes with standard chemotherapy.4

At the time of this analysis, the safety profile of BRAFTOVI + MEKTOVI was consistent with previous findings. The most common (≥30%) treatment-related adverse events were nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%).

"These long-term survival results reinforce Pfizer’s unwavering commitment to improving outcomes in lung cancer," said Jeff Legos, Chief Oncology Officer, Pfizer. "The findings provide hope for treatment-naïve BRAF V600E mNSCLC patients and their families and underscore the importance of advancing therapies that can provide a sustained impact for patients."

The Phase 2 PHAROS trial (NCT03915951) is an open-label, multicenter, single-arm study examining BRAFTOVI + MEKTOVI combination therapy in treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. BRAFTOVI + MEKTOVI was approved by the U.S. Food and Drug Administration (FDA) in October 2023, and by the European Commission in August 2024, for the treatment of BRAF V600E-mutant metastatic NSCLC based on the initial objective response rate (ORR; the primary endpoint) and duration of response (secondary endpoint) results from the PHAROS trial. The ORR was 75% (95% CI: 62, 85) for treatment-naïve patients (n=59) and 46% (95% CI: 30, 63) for previously treated patients (n=39).

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.

About BRAF V600E-mutant non-small cell lung cancer (NSCLC)

NSCLC treatment has dramatically evolved, enabling more individualized treatment options based on molecular profiles and immunologic status. BRAF mutations exemplify this precision medicine opportunity—while BRAF V600E mutations occur in only about 2% of NSCLC cases,3 they represent approximately half of all BRAF-mutant metastatic NSCLC.5 Targeting BRAF offers potential to inhibit tumor growth and proliferation driven by these specific mutations.6

Despite this evolution, unmet needs remain for advanced disease. Approximately one in six patients with advanced NSCLC have no biomarker testing results prior to first-line treatment.7 Among tested patients, many do not receive targeted therapy or have limited to no options available for targeted therapy.8-10

About BRAFTOVI (encorafenib) + MEKTOVI (binimetinib)

BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E, and MEKTOVI is an oral small molecule MEK inhibitor, both of which target key proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in certain cancers, including melanoma, CRC, and NSCLC.

Pfizer has exclusive rights to BRAFTOVI + MEKTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize both products in Japan and South Korea, Medison has exclusive rights in Israel and Pierre Fabre Laboratories has exclusive rights in all other countries, including Europe and Asia (excluding Japan and South Korea). The PHAROS trial is conducted with support from Pierre Fabre.

INDICATION AND USAGE

WARNINGS AND PRECAUTIONS

New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous, can occur. In the PHAROS trial, cutaneous squamous cell carcinoma (cuSCC) and skin papilloma (SP), each occurred in 2% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies. Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms. Monitor patients receiving BRAFTOVI for signs and symptoms of non-cutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment.

Tumor Promotion in BRAF Wild-Type Tumors: In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells exposed to BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation using an FDA-approved test prior to initiating BRAFTOVI.

Cardiomyopathy: Cardiomyopathy manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. In the PHAROS trial, evidence of cardiomyopathy occurred in 11% and Grade 3 left ventricular dysfunction occurred in 1% of patients. Cardiomyopathy resolved in 82% of patients. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multi-gated acquisition (MUGA) scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN). Patients with cardiovascular risk factors should be monitored closely. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Hepatotoxicity: Hepatotoxicity can occur when MEKTOVI is administered in combination with BRAFTOVI. In the PHAROS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 10% for aspartate aminotransferase (AST), 9% for alanine aminotransferase (ALT), and 3.2% for alkaline phosphatase. Monitor liver laboratory tests before initiation of BRAFTOVI and MEKTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Rhabdomyolysis: Rhabdomyolysis can occur when MEKTOVI is administered in combination with BRAFTOVI. In the PHAROS trial, elevation of laboratory values of serum creatine kinase (CK) occurred in 41% of patients. No patient experienced rhabdomyolysis. Monitor CPK and creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Hemorrhage: Hemorrhage can occur when BRAFTOVI is administered in combination with MEKTOVI. In the PHAROS trial, hemorrhage occurred in 12% of patients, including fatal intracranial hemorrhage (1%); Grade 3 or 4 hemorrhage occurred in 4.1% of patients. The most frequent hemorrhagic events were anal hemorrhage and hemothorax (2% each). Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Venous Thromboembolism (VTE): In the PHAROS trial, VTE occurred in 7% of patients, including 1% of patients who developed pulmonary embolism. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Ocular Toxicities: In the PHAROS trial, serous retinopathy (retinal detachment) occurred in 2% of patients with no cases of blindness. Retinal vein occlusion (RVO) is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated with MEKTOVI in combination with BRAFTOVI. The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. Perform ophthalmological evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue MEKTOVI in patients with documented RVO. Uveitis, including iritis and iridocyclitis, was reported in patients treated with MEKTOVI in combination with BRAFTOVI. In PHAROS, uveitis occurred in 1% of patients. Assess for visual symptoms at each visit. Perform an ophthalmological evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

QT Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. In the PHAROS trial, an increase in QTcF to >500 ms was measured in 2.1% (2/95) of patients who received BRAFTOVI with MEKTOVI. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

Interstitial Lung Disease (ILD): In the PHAROS trial, 1 patient (1%) receiving MEKTOVI with BRAFTOVI developed pneumonitis. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Embryo-Fetal Toxicity: BRAFTOVI and MEKTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Effective, non-hormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI with MEKTOVI.

Risks Associated with BRAFTOVI as a Single Agent: There is an increased risk of certain adverse reactions compared to when BRAFTOVI is used in combination with MEKTOVI. If MEKTOVI is temporarily interrupted or permanently discontinued, reduce the dose of BRAFTOVI as recommended.

Risks Associated with Combination Treatment: BRAFTOVI is indicated for use as part of a regimen in combination with MEKTOVI. Refer to the prescribing information for BRAFTOVI and MEKTOVI for additional risk information.

Lactation: Advise women not to breastfeed during treatment with BRAFTOVI and MEKTOVI and for 2 weeks after the final dose.

Infertility: Advise males of reproductive potential that BRAFTOVI may impair fertility.

ADVERSE REACTIONS

The most common adverse reactions (≥25%, all grades, in the PHAROS trial) for BRAFTOVI with MEKTOVI were: fatigue (61%), nausea (58%), diarrhea (52%), musculoskeletal pain (48%), vomiting (37%), abdominal pain (32%), visual impairment (29%), constipation (27%), dyspnea (27%), rash (27%), and cough (26%).

Serious adverse reactions occurred in 38% of patients receiving BRAFTOVI with MEKTOVI. Serious adverse reactions (≥2% of patients in the PHAROS trial) were hemorrhage (6%), diarrhea (4.1%), anemia (3.1%), dyspnea (3.1%), pneumonia (3.1%), arrhythmia (2%), device related infection (2%), edema (2%), myocardial infarction (2%), and pleural effusion (2%). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage (1%) and myocardial infarction (1%).

Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI with MEKTOVI in the PHAROS trial were peripheral neuropathy, dysgeusia, facial paresis, pancreatitis, hyperkeratosis, erythema, photosensitivity, and drug hypersensitivity.

In the PHAROS trial, the most common laboratory abnormalities (all grades) (≥20%) for BRAFTOVI and MEKTOVI included increased creatinine (91%), hyperglycemia (48%), anemia (47%), increased creatine kinase (41%), lipase increased (40%), increased ALT (34%), hypoalbuminemia (32%), increased alkaline phosphatase (31%), increased AST (31%), hyperkalemia (31%), hyponatremia (26%), lymphopenia (24%), serum amylase increased (22%), and thrombocytopenia (20%).

DRUG INTERACTIONS

Strong or moderate CYP3A4 inhibitors: Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors, including grapefruit juice. If coadministration is unavoidable, reduce the BRAFTOVI dose.

Strong CYP3A4 inducers: Avoid coadministration of BRAFTOVI with strong CYP3A4 inducers.

Sensitive CYP3A4 substrates: Avoid the coadministration of BRAFTOVI with CYP3A4 substrates (including hormonal contraceptives) for which a decrease in plasma concentration may lead to reduced efficacy of the substrate. If the coadministration cannot be avoided, see the CYP3A4 substrate product labeling for recommendations.

Dose reductions of drugs that are substrates of OATP1B1, OATP1B3, or BCRP may be required when used concomitantly with BRAFTOVI.

Avoid coadministration of BRAFTOVI with drugs known to prolong QT/QTc interval.

The information above applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted. See full Prescribing Information for BRAFTOVI and for MEKTOVI for dose modifications for adverse reactions.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information.

(Press release, Pfizer, OCT 19, 2025, View Source [SID1234656808])

On October 19, 2025 iOncologi, Inc., a biotechnology company developing next-generation RNA-based cancer immunotherapies, reported that the United States Patent and Trademark Office (USPTO) has granted a U.S. patent for a novel method using RNA-based formulations to enhance tumor responsiveness to immune checkpoint inhibitor (ICI) therapy.

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The patent, owned by the University of Florida Research Foundation (UFRF) and exclusively licensed to iOncologi, further consolidates the intellectual-property portfolio supporting the company’s UNIFYRs (UNiversal Immune FortifYing RNAs) platform — an innovative approach that leverages RNA-driven immune reprogramming to restore and amplify checkpoint inhibitor efficacy across multiple solid-tumor types.

"This patent grant highlights the pioneering RNA therapeutics emerging from the University of Florida that have the potential to fundamentally reshape solid tumor treatment," said Dr. Duane Mitchell, co-inventor and co-founder of iOncologi. "By demonstrating that a single RNA backbone can restore responsiveness to immune checkpoint inhibitors across multiple tumor types, we are charting a course toward a universal strategy to overcome immune resistance in cancer and unlock responses in patients who currently do not benefit from immunotherapy."

Scientific Validation in Nature Biomedical Engineering

The newly granted patent builds on discoveries published earlier this year in Nature Biomedical Engineering (Qdaisat, S., et al. Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading. Nat. Biomed. Eng 9, 1437–1452 [2025]).

The study, led by researchers at the University of Florida, revealed how non–tumor-antigen-specific mRNA formulations can amplify early type-I interferon responses and trigger epitope spreading — a mechanism that reprograms the tumor microenvironment and restores sensitivity to ICIs.

"The findings reported in Nature Biomedical Engineering offer detailed mechanistic insight that underpins the claims in this newly granted patent," said Dr. Elias Sayour, Professor of Neurosurgery and Pediatrics at the University of Florida, co-inventor, and senior author of the study. "By demonstrating that non-antigen-encoding, systemically delivered mRNA-lipid formulations can re-educate both innate and adaptive immunity, we’re establishing the biological basis that underlies iOncologi’s UNIFYRs platform."

(Statements regarding University of Florida research are factual and provided for illustrative and contextual purposes only.)

Clinical Data Presented at ESMO (Free ESMO Whitepaper) 2025

Supporting this mechanistic foundation, new translational data were presented by Dr. Adam Grippin of MD Anderson Cancer Center on Sunday, October 19, 2025 (LBA54) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress in Berlin.

The presentation, titled "SARS-CoV-2 mRNA vaccines sensitize tumors to immune checkpoint blockade," reported that mRNA-based immune activation, achieved through SARS-CoV-2 mRNA vaccination, correlated with significantly improved overall survival among checkpoint-treated melanoma and non–small cell lung cancer (NSCLC) patients — findings that closely reflect the mechanistic principles first described in Nature Biomedical Engineering and have been independently reported in mainstream media, including NBC News, for their potential to enhance immunotherapy response in cancer patients.

(Statements referencing presentations by MD Anderson Cancer Center investigators are factual and provided for illustrative and contextual purposes only.)

"These findings represent a turning point for patients facing immunotherapy resistance," said Edgardo Rodriguez-Lebron, PhD, Chief Executive Officer of iOncologi, Inc. "The implications extend well beyond patient outcomes — RNA-based immune activation could revitalize immune checkpoint inhibitor franchises that have struggled to show benefit in solid tumors. With this foundation in place, iOncologi aims to work with strategic partners to accelerate the path to patients."

Advancing the UNIFYRs Platform

With this newly granted patent, iOncologi further strengthens its leadership in RNA-based immune reprogramming. The UNIFYRs platform is designed to fortify and broaden ICI efficacy across multiple tumor types, representing a new therapeutic modality positioned at the intersection of oncology, RNA technology, and systems immunology.

(Press release, iOncologi, OCT 19, 2025, View Source [SID1234656793])

On October 19, 2025 Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class cancer therapies targeting the Hippo pathway, reported new data from the company’s ongoing Phase 1/2 clinical trial of its first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989. Findings demonstrated notable antitumor activity for VT3989 in refractory mesothelioma patients, along with a manageable safety and tolerability profile. Based on these positive study results, Vivace plans to advance VT3989 into a registrational Phase 3 trial in mesothelioma in the first half of 2026. The findings were the focus of an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025, as well as a peer-reviewed paper in Nature Medicine that was published concurrently with the ESMO (Free ESMO Whitepaper) presentation.

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The presentation highlighted a cohort of 22 refractory mesothelioma patients treated with the optimized Phase 3 dose and schedule for VT3989. Key findings for VT3989 in this population include:

Objective Response Rate (ORR) of 32% (7 of 22 patients achieved a partial response).

Disease Control Rate (DCR) of 86% (19 of 22 patients achieved a partial response or stable disease).

Median Progression-Free Survival (PFS) of 40 weeks, which is more than double the 15-week benchmark for standard-of-care salvage chemotherapy.
Study results showed VT3989 treatment to be safe and well tolerated with no dose-limiting toxicities in 172 patients across dose escalation and dose expansion cohorts. The majority of reported adverse events (AEs) were categorized as mild or moderate in severity and the discontinuation rate due to AEs was low (3.5%). The most commonly reported treatment-related AEs were low grade fatigue, proteinuria (a reversible increase of protein in the urine), and swelling in the extremities. The total number of patients experiencing Grade 3/4 treatment-related AEs was low at 15 (8.7%).

"These findings make a compelling case for the therapeutic potential of VT3989 in the treatment of mesothelioma, a cancer that presents significant treatment challenges and for which there are few therapeutic options beyond first‑line therapies" said Timothy A. Yap, M.B.B.S.., Ph.D., Head of Clinical Development in the Therapeutics Discovery Division at the University of Texas MD Anderson Cancer Center and lead clinical investigator for the study. "We are encouraged by the clinically meaningful disease control that was achieved with VT3989, especially in these heavily pretreated patients. We believe that the strength of these efficacy findings, combined with the encouraging safety profile demonstrated in the study, support the advancement of VT3989 into a registrational clinical trial for mesothelioma."

The ongoing Phase 1/2 study (View Source) is a multi-center, open label trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and biological activity of VT3989 in patients with refractory metastatic solid tumors, including refractory mesothelioma. The mesothelioma patients treated with the optimized Phase 3 dose represented a heavily pre-treated patient population, with all having received immunotherapy and 82% having received chemotherapy.

"It is gratifying to share these positive study data, particularly considering how much hard work our team has undertaken in not only developing a first-in-class therapy against a novel target, but doing so in a notoriously hard-to-treat cancer," said Neelesh Sharma, M.D., Ph.D., chief medical officer of Vivace. "Demonstrating such a clear and substantial benefit compared to salvage chemotherapy benchmarks gives us great confidence as we prepare to advance VT3989 into a Phase 3 program. We are committed to bringing this first-in-class therapy to patients who are in desperate need of new treatment options."

VT3989 was recently awarded Orphan Drug Designation and Fast Track Designation by the United States Food and Drug Administration for the treatment of mesothelioma. The Fast Track Designation specifically applies to the treatment of patients with unresectable malignant non-pleural or pleural mesothelioma whose disease has progressed on prior immune checkpoint inhibitor therapy and platinum-based chemotherapy.

The ESMO (Free ESMO Whitepaper) presentation will be available on Vivace’s website at www.vivacetherapeutics.com following the conference. The Nature Medicine paper can be accessed on the publication’s website at www.nature.com/nm/.

(Press release, Vivace Therapeutics, OCT 19, 2025, View Source [SID1234656795])

On October 19, 2025 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported data from a new ad hoc analysis from the IGNYTE phase 2 cohort of RP1 plus nivolumab was presented by Caroline Robert, M.D., Ph.D., at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 being held in Berlin (Poster 1644P).

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The analysis of acral melanoma patients from the IGNYTE clinical trial showed treatment with RP1 combined with nivolumab resulted in an objective response rate of 44% (8/18) with a median duration of response of 11.9 months (3.9, not reached). The safety profile was favorable with generally transient grade 1 and 2 treatment related adverse events.

Acral melanoma is a rare and aggressive type of cutaneous melanoma (2-3% of all melanoma cases) that frequently occurs on the palms of the hands, soles of the feet, and nailbeds, and often has poor outcomes with many patients presenting with in-transit metastases. Acral melanoma does not typically respond well to available therapies, such as immune checkpoint inhibitors. Following progression on first-line therapy, aside from targeted therapy for a subset of patients with BRAF mutation-positive tumors, few viable treatment options exist.

The IGNYTE-3 randomized controlled phase 3 trial evaluating RP1 plus nivolumab versus physician’s choice of treatment in melanoma that has progressed on anti-PD1 and anti-CTLA-4 therapy is currently recruiting.

An additional poster titled, "Efficacy and safety of RP1 + nivolumab in patients with non-melanoma skin cancers (NMSC)" is also being presented at ESMO (Free ESMO Whitepaper) by Dirk Schadendorf, M.D. (Poster 1661P).

About IGNYTE
The IGNYTE phase 2 cohort enrolled 140 patients with stage IIIB-IV cutaneous melanoma and confirmed progression on anti-PD1- based therapy for > 8 weeks as the last prior treatment. RP1 was administered intratumorally into superficial and/or deep/visceral tumors once every 2 weeks for up to 8 doses (≤10 mL per cycle) with intravenous nivolumab (240 mg); nivolumab was then given alone (240 mg every 2 weeks or 480 mg every 4 weeks) for up to 2 years, with further RP1 allowed if indicated.

About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF, intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

(Press release, Replimune, OCT 19, 2025, View Source [SID1234656778])

On October 19, 2025 Johnson & Johnson (NYSE:JNJ) reported promising new results from the Phase 1b/2 OrigAMI-4 study evaluating the efficacy and safety of subcutaneous (SC) amivantamab monotherapy in patients with human papillomavirus (HPV)-unrelated, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after disease progression on a checkpoint inhibitor and platinum-based chemotherapy. The study used the new subcutaneous formulation of amivantamab, which can be delivered in a five-minute manual injection, offering increased patient convenience compared to intravenous RYBREVANT (amivantamab-vmjw). Data were presented during a mini-oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress (Oral Abstract #1327MO).1

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Patients with R/M HNSCC have limited options and poor outcomes after disease progression on a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy.2 Many are unable to receive further treatment, and for those who do, response rates with available therapies are typically only 10 to 24 percent.2,3,4 Survival remains short, with a median of 6 to 9 months, and may be even shorter among patients with HPV-unrelated disease.2,4,5,6 Patients also face a significant burden of symptoms such as difficulty swallowing, impaired speech, pain and fatigue.2 Epidermal growth factor receptor (EGFR) and MET, two key tumor drivers, are overexpressed in 80 to 90 percent of HNSCC tumors, highlighting their role as potential treatment targets.7,8,9 RYBREVANT, the world’s first bispecific antibody approved for lung cancer, inhibits EGFR and MET, in addition to activating the immune system to attack cancer cells.10

"Patients with recurrent or metastatic head and neck cancer face an aggressive disease that significantly impacts their quality of life," said Professor Kevin Harrington*, MBBS, Ph.D., Professor in Biological Cancer Therapies at The Institute of Cancer Research, Royal Marsden Hospital, London, UK, and primary study investigator. "These results represent one of the most encouraging response rates we’ve seen in this difficult-to-treat setting, with durability that could meaningfully extend the time patients live without their disease progressing."

In Cohort 1 of the OrigAMI-4 study, treatment with SC amivantamab resulted in an overall response rate (the primary endpoint) of 45 percent in 38 efficacy-evaluable patients with R/M HNSCC unrelated to HPV with disease progression on or after a PD-1 or PD-L1 checkpoint inhibitor and platinum-based chemotherapy (95 percent confidence interval [CI], 29-62).1 Responses occurred quickly, with a median time to first response of 6.4 weeks (range, 5.7-18.3), and were durable, with a median duration of response of 7.2 months (95 percent CI, 5.3-not estimable [NE]).1,11 Tumor shrinkage of target lesions was observed in 82 percent of patients after 8.3 months follow-up.1 Median progression-free survival was 6.8 months (95 percent CI, 4.2-9.0), while median overall survival had not yet been reached (95 percent CI, 7.7-NE).1

"These data highlight the broader potential of RYBREVANT-based therapies across solid tumors where the EGFR and/or MET pathways are activated," said Kiran Patel, Vice President, Global Head, Solid Tumor Clinical Development and Diagnostics, Johnson & Johnson Innovative Medicine. "RYBREVANT combinations have already demonstrated significant results for certain patients with non-small cell lung cancer, leading to extended survival and delayed treatment resistance. Now we’re building on that progress in other hard-to-treat diseases like head and neck cancer. By targeting EGFR and MET while also engaging the immune system, subcutaneous amivantamab could provide new options for more patients who have few effective treatments."

The safety-evaluable population included 86 patients who received at least one dose of SC amivantamab monotherapy. The safety profile was consistent with prior SC amivantamab monotherapy studies, with no new safety signals observed. The most common treatment-emergent adverse events were fatigue (31 percent), hypoalbuminemia (31 percent) and stomatitis (23 percent). Administration-related reactions occurred in seven percent of patients, all mild to moderate (grade 1-2), with no severe events. Treatment discontinuation due to treatment-related adverse events occurred in two percent of patients.1

Based on these results, Johnson & Johnson is initiating further study of SC amivantamab in head and neck cancer with the Phase 3 OrigAMI-5 study, which is evaluating first-line SC amivantamab with pembrolizumab and carboplatin versus 5-fluorouracil (5FU) plus pembrolizumab and platinum-based chemotherapy (cisplatin or carboplatin) in patients with HPV-unrelated R/M HNSCC. In addition to supporting further evaluation in first-line R/M HNSCC, these findings add to the evidence supporting the role of RYBREVANT-based treatments across multiple solid tumors, including non-small cell lung cancer, colorectal cancer and HNSCC.

About the OrigAMI-4 Study

OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study evaluating SC amivantamab in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes five cohorts, including Cohort 1, which studied SC amivantamab as monotherapy in patients with human papillomavirus (HPV)-unrelated R/M HNSCC who had received prior platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Patients with prior anti-EGFR therapy were excluded. Subcutaneous amivantamab was administered every three weeks (Q3W) at 2400 mg, or 3360 mg for patients weighing 80 kg or more. The primary endpoint is overall response rate (ORR), assessed by blinded independent central review (BICR) using RECIST v1.1**.12

About Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer, accounting for more than 90 percent of cases and approximately 4.5 percent of all cancers worldwide.13 It develops in the mucosal linings of the oral cavity, oropharynx, hypopharynx, and larynx.13 Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).13 Around 75 percent of cases are HPV-negative, which is typically associated with a poorer prognosis and reduced response to treatment.13,14 Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients are diagnosed at an advanced stage, and recurrent or metastatic HNSCC continues to carry a poor prognosis.2,7

About Subcutaneous Amivantamab

Subcutaneous amivantamab is an investigational fixed-dose combination of the bispecific antibody amivantamab and recombinant human hyaluronidase PH20 (rHuPH20), which is part of Halozyme’s ENHANZE drug delivery technology. It targets EGFR and MET with immune cell-directing activity and is being developed to address tumors driven by activating and resistance EGFR mutations as well as MET alterations.

Subcutaneous amivantamab is being studied across multiple tumor types, including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC).

About RYBREVANT

RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy 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.10

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (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.

RYBREVANT is approved in the U.S., Europe and other markets around the world 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.

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI.

Subcutaneous amivantamab is approved in Europe in combination with LAZCLUZE for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. A Biologics License Application (BLA) was submitted to the U.S. FDA for this indication.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion, exon 19 deletion and L858R variants. The NCCN Guidelines include:

Amivantamab-vmjw (RYBREVANT) plus lazertinib (LAZCLUZE) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.15†‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.15 †‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC. 15 †‡
Amivantamab-vmjw (RYBREVANT) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC. 15 †‡
In addition to the Phase 1b/2 OrigAMI-4 study, RYBREVANT is being studied in multiple clinical trials, including:

The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with LAZCLUZE versus osimertinib and versus LAZCLUZE alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations.16
The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT (with or without LAZCLUZE) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations after disease progression on or after osimertinib.17
The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.18
The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE with subcutaneous (SC) amivantamab compared to RYBREVANT in patients with EGFR-mutated advanced or metastatic NSCLC.19
The Phase 2 PALOMA-2 (NCT05498428) study assessing SC amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.20
The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of SC amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for SC amivantamab delivery.21
The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in patients with advanced NSCLC.22
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT in combination with LAZCLUZE and LAZCLUZE as a monotherapy in patients with advanced NSCLC with EGFR mutations.23
The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC.24
The Phase 1/2 swalloWTail (NCT06532032) study assessing RYBREVANT and docetaxel combination therapy in patients with metastatic NSCLC.25
The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.26
The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT in combination with LAZCLUZE in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.27
The Phase 2 COPERNICUS (NCT06667076) study combining developments in treatment administration and prophylactic supportive care in representative US patients with common EGFR-mutated NSCLC treated with SC amivantamab in combination with LAZCLUZE or chemotherapy.28
The Phase 2 COCOON (NCT06120140) study assessing the effectiveness of a proactive dermatologic management regimen given with first-line RYBREVANT and LAZCLUZE in patients with EGFR-mutated advanced NSCLC.29
The Phase 1b/2 OrigAMI-1 (NCT05379595) study assessing RYBREVANT monotherapy and in addition to standard-of-care chemotherapy in patients with advanced or metastatic colorectal cancer.30
The legal manufacturer for RYBREVANT is Janssen Biotech, Inc.

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RYBREVANT IMPORTANT SAFETY INFORMATION 10

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

RYBREVANT can cause infusion-related reactions (IRRs) 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. The incidence of infusion modifications was 46%, and 2.8% of patients permanently discontinued RYBREVANT due to IRR.

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. The incidence of infusion modifications was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRRs.

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 can cause severe and fatal interstitial lung disease (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 (0.2%) 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). For patients receiving RYBREVANT in combination with LAZCLUZE, immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic Events with Concomitant Use of RYBREVANT and LAZCLUZE

RYBREVANT in combination with LAZCLUZE can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism (PE). Most events occurred during the first four months of therapy.

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 and LAZCLUZE based on severity. Once anticoagulant treatment has been initiated, resume 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 and continue treatment with LAZCLUZE at the same dose level at the discretion of the healthcare provider.

Dermatologic Adverse Reactions

RYBREVANT can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.

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%).

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT or LAZCLUZE in combination with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin.

When initiating treatment, administer alcohol-free emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (eg, use of oral antibiotics). If skin reactions develop, start 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 in combination with LAZCLUZE, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity

RYBREVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.

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 with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.

Embryo-Fetal Toxicity

Based on animal models, RYBREVANT and LAZCLUZE can cause fetal harm when administered to a pregnant woman. Advise 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, and for 3 weeks after the last dose of LAZCLUZE.

ADVERSE REACTIONS

RYBREVANT with LAZCLUZE

In MARIPOSA (n=421) , the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (RYBREVANT) (63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), and nausea (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).

Serious ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT) (2.1% each). Fatal ARs occurred in 7% of patients due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).

RYBREVANT with Carboplatin and Pemetrexed

In MARIPOSA-2 (n=130), the most common ARs (≥20%) were rash (72%), IRRs (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).

In MARIPOSA-2, serious ARs occurred in 32% of patients, with those occurring in >2% of patients including dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and PE (2.3%). Fatal ARs occurred in 2.3% of patients; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).

In PAPILLON (n=151), the most common ARs (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), IRRs (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

In PAPILLON, serious ARs occurred in 37% of patients, with those occurring in ≥2% of patients including rash, pneumonia, ILD, PE, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.

RYBREVANT as a Single Agent

In CHRYSALIS (n=129), the most common ARs (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Serious ARs occurred in 30% of patients, with those occurring in ≥2% of patients including PE, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.

LAZCLUZE Drug Interactions

Avoid concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

(Press release, Johnson & Johnson, OCT 19, 2025, View Source [SID1234656796])