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Milk has around 350 particles per kilogram, while cheese contains at least 1,000 per kilogram. PET, polyethene and polypropylene are the common plastics, which are generally found in packaging, which could be the reason behind contamination. But…
212Pb-DOTAMTATE (AlphaMedix) showed clinically meaningful antitumor activity with sustained and durable responses along with a manageable safety profile in patients with peptide receptor radionuclide therapy (PRRT)-exposed, somatostatin receptor (SSTR)-positive, unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to results from the ALPHAMEDIX-02 trial (NCT05153772).1
Per investigator review, the objective response rate (ORR) was 34.6% (9/26 patients), consisting of all partial responses. None of the responders had progressed at the time of the data cutoff. Sixteen patients (61.5%) had stable disease for a disease control rate of 96.2% (95% CI, 80.4%-99.9%). There was 1 patient with progressive disease. The ORR per blinded independent central review was 19.2% and the disease control rate was 100%.
The investigator-assessed 18-month progression-free survival (PFS) and overall survival (OS) rates were 82.6% (59.0-93.3) and 85.1% (58.5%-95.2%), respectively. The PFS per BICR was 88.0% (95% CI, 67.3%-96.0%).
212Pb-DOTAMTATE was determined by investigators to have an acceptable side effect profile, with the majority of treatment-emergent adverse events (TEAEs) being grade 1 or 2.
“The pivotal phase 2 ALPHAMEDIX-02 study presents a favorable benefit/risk profile of 212Pb-based targeted alpha therapy in radioligand therapy (RLT)-exposed patients with advanced GEP-NETS where few effective treatment options are available,” said lead study author Jonathan Strosberg, MD,a professor and leader of the Neuroendocrine Tumor Division and the Department of Gastrointestinal Oncology Research Program at Moffitt Cancer Center.
“Effective treatment options are limited for patients with GEP-NETs whose disease progresses after PRRT with beta-emitting 177Lu-labelled somatostatin analogs (SSA),” said Strosberg.
Accordingly, Strosberg et al explored the next-generation SSTR-targeted RLT 212Pb-DOTAMTATE in this patient population. 212Pb-DOTAMTATE “utilizes the high-energy and shorter-range alpha emission, which leads to highly effective dsDNA breakage and may result in more targeted oncologic effects,” explained Strosberg.
Overall, the open-label, multicenter, phase 2 ALPHAMEDIX-02 study explored 212Pb-DOTAMTATE in patients with both PRRT-naïve (cohort 1) and PRRT-exposed (cohort 2) metastatic GEP-NETs that was histologically confirmed, had positive SSA imaging, and had at least 1 site of measurable disease.
Previously reported data for cohort 1 showed that 212Pb-DOTAMTATE achieved an ORR of 54.3% and a manageable safety profile in PRRT-naïve patients. Results for PRRT-exposed patients (cohort 2) were shared by Strosberg at ESMO.
Cohort 2 comprised 26 PRRT-exposed patients who had progressive disease following treated with up to 4 doses of 177Lu-SSA. Patients had received their last 177Lu-SSA dose at least 6 months before the trial. All patients received 212Pb-DOTAMTATE at 67.6 μCi/kg every 8 weeks for up to 4 cycles. The primary end point was ORR (RECIST1.1) and safety. Secondary outcome measures included progression free survival and overall survival.
“212Pb-DOTAMTATE demonstrated an acceptable side effect profile, where most (57.7%) treatment-emergent adverse events (TEAEs) were grade 1 or 2, allowing the majority (84.6%) of patients to complete all 4 doses and 0 TEAEs leading to treatment discontinuation,” said Strosberg.
The most common grade 1/2 TEAEs were alopecia (84.6%), fatigue (76.9%), nausea (69.2%), diarrhea (38.5%), dysphagia (34.6%), vomiting (30.8%), decreased appetite (30.8%), abdominal pain (26.9%), and lymphopenia (23.1%).
Eleven patients (42.3%) experienced grade ≥3 TEAEs. These included lymphopenia (n = 4), dysphagia (n = 3), vomiting (n = 2), deceased appetite (n = 1), and fatigue (n = 1). Five patients had treatment-emergent serious adverse events and there were no TEAE-related patient deaths.
Specifically focusing on dysphagia, Strosberg explained that the condition emerged as a chronic toxicity which was “kind of a surprising side effect––it’s not something that we anticipated when we started this trial.” He added, “Manometry may demonstrate esophageal dysmotility in patients with dysphagia. Botox injection to the lower esophageal sphincter provides relief in many cases and some patients have required minimally-invasive surgery.”
The mean patient age was 61.8 years and the median time since diagnosis was 7.2 years (range, 2.8-18.8). Over three-fourths of patients had grade 1 or 2 disease. The primary tumor sites were the pancreas and small intestine at 11 patients each. All patients had prior RLT, 96.2% had prior SSAs, and 88.5% had surgical resection prior to enrollment. Further, 15 patients had received chemotherapy, 15 had received TKIs, 7 had embolization, and 5 had received EBRT.
In a press release reporting these results, Christopher Corsico, MD, Global Head of Development at Sanofi, which codevelops 212Pb-DOTAMTATE with Orano Med, stated, “The promising ALPHAMEDIX-02 results represent a significant step forward, reinforcing the potential of targeted alpha therapy to deliver precise treatment for GEP-NETs.”2
Corsico added, “These data, demonstrating clinically meaningful activity and a manageable safety profile, underscore our unrelenting commitment to developing innovative therapies for patients with difficult-to-treat cancers. We look forward to advancing [212Pb-DOTAMTATE] and working with Orano Med and regulators to bring this important treatment to the GEP-NET community as soon as possible.”
References
Marvel Rivals will debut its first zombie-themed PVE survival mode on October 23, starring several Marvel heroes
Marvel Rivals will receive its first…
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I…
Findings from the CAPItello-281 trial (NCT04493853) presented at the 2025 European Society for Medical Oncology (ESMO) Congress showed that the combination of the oral AKT inhibitor capivasertib (Truqap) plus abiraterone acetate, prednisone, and androgen deprivation therapy (ADT) extended radiographic progression-free survival (rPFS) by 7.5 months compared with abiraterone acetate, prednisone, ADT, and placebo in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC).1
After a median follow-up of 18.4 months, the median rPFS with the addition of capivasertib was 33.2 months (95% CI, 25.9–44.2) compared with 25.7 months (95% CI, 22.0–29.9) for placebo (HR, 0.81; 95% CI, 0.66–0.98; P = .034). Median overall survival (OS) was not yet reached at the time of the analysis for either arm. There had been 267 events at the time of the assessment, with 129 in the capivasertib arm and 138 in the placebo group (HR, 0.90; 95% CI, 0.71–1.15; P = .401).
“The primary end point was met, showing a statistically significant rPFS benefit with the combination of capivasertib and abiraterone, with consistent benefits observed across clinical end points,” lead investigator Karim Fizazi, MD, PhD, a medical oncologist at Institut Gustave Roussy and Centre Oscar Lambret, said during a presentation of the results. “The rPFS in the control arm was only 25.7 months, highlighting the poor prognosis of a PTEN population.”
In the CAPItello-281 trial, 1012 patients were treated with abiraterone acetate at 1000 mg with prednisone at 5 mg daily plus ADT. Patients were randomly selected to receive capivasertib at 400 mg twice daily for 4 days on and 3 days off (n = 507) or a matched placebo (n = 505). PTEN deficiency was defined as more than 90% of malignant cells with no specific cytoplasmic staining by IHC. Of those screened, approximately 25% matched these requirements.
The primary end point of the study was investigator-assessed rPFS. Secondary end points included overall survival (OS). The analysis presented at ESMO was the final analysis for rPFS. A final OS analysis is still planned.
The baseline characteristics were similar between groups. In the capivasertib and placebo arms, respectively, the median ages were 67 and 68 years. The total Gleason score was 8 or more for 78.5% and 79% of patients and the disease risk was high for 61.3% and 65.9% of those in the capivasertib and placebo groups, respectively. The primary location of disease metastases was the bone for 91.1% and 92.5% in the investigational and control arms, respectively. Nearly two-thirds of patients had an ECOG performance score of 0 with the remainder having a score of 1. Nearly three-fourths of patients had high volume disease.
“Consistent with the poor prognosis of this PTEN-deficient prostate cancer population, most patients had high-risk, high-volume, high Gleason score disease,” said Fizazi.
In prespecified subgroup analyses, similar improvements in rPFS were seen with the addition of capivasertib, although none passed the bar for statistical significance. In those with high-volume disease with visceral metastases, the hazard ratio was 0.77 favoring the capivasertib arm (95% CI, 0.52–1.14) and in those with a Gleason score of 8 or more the hazard ratio was 0.82 (95% CI, 0.65–1.02). In those with a score lower than 8, the hazard ratio was 1.06 (95% CI, 0.66–1.69).
The time to next treatment was 37.0 months with capivasertib compared with 28.5 months with placebo (95% CI, 0.75–1.11). The median symptomatic skeletal event-free survival was 42.5 months with capivasertib compared with 37.3 months for placebo. Events for this end point included pathological fracture, spinal cord compression, use of radiation, surgical intervention, and death. There were 150 of these events in the capivasertib group and 176 in the placebo group (HR, 0.82; 95% CI, 0.66–1.02; P = .079).
“Roughly half of patients are still on drug and another analysis of overall survival is planned at another time cutoff,” Fizazi said. “There was a numerical improvement of 5.2 months prolongation in event-free survival in the capivasertib arm.”
The time to castration resistance was 29.5 months in the capivasertib group and 22.0 months for placebo (HR, 0.77; 95% CI, 0.63–0.94). For this study, Fizazi noted, castration resistance was defined as radiographic disease progression, PSA progression, and development of a skeletal event. The median time to PSA progression was not calculable at the time of the analysis, with 60 events recorded in the capivasertib arm compared with 82 in the placebo group (HR, 0.73; 95% CI, 0.52-1.01). Pain progression was still too early to measure, as too few events had occurred.
“Interestingly, the Kaplan-Meier curves for time to PSA progression defined by PCWG3 are much higher than those for time to castration resistance, indicating that many patients with PTEN loss tend to first experience a detrimental clinical event, such as an imaging-based progression or bone mobility, prior to a PSA rise of greater than 25%,” said Fizazi.
Additional analyses were completed looking at different PTEN expression levels, following the suggestion of an impact from other studies looking at AKT inhibitors. Of those with PTEN loss on 95% of cells or more, the median rPFS was 33.2 months with capivasertib and 22.7 months with placebo (HR, 0.75; 95% CI, 0.60-0.94). When PTEN loss was 99% or more, the median rPFS was 34.1 months with capivasertib vs 22.4 months for placebo (HR, 0.71; 95% CI, 0.52-0.97). When there was 100% PTEN loss, the median rPFS was 34.1 months compared with 22.1 months for capivasertib and placebo, respectively (HR, 0.68; 95% CI, 0.48–0.96).
“In the capivasertib arm, we see strongly consistent rPFS irrespective of the degree of PTEN deficiency; however, with increasing PTEN deficiency there is worsening prognosis in the control arm,” said Fizazi. “The same phenomenon of increasing treatment effect was also seen for overall survival.” For those with 100% PTEN loss, the early hazard ratio for OS was 0.77 (95% CI, 0.51–1.14).
The increase in treatment benefit was also seen across all secondary end points, when assessing higher levels of PTEN loss. At 100% PTEN loss, the hazard ratio for symptomatic skeletal event-free survival was 0.70 favoring capivasertib (95% CI, 0.48–1.01). For time to castration resistance the hazard ratio was 0.63 (95% CI, 0.45–0.89) and for time to PSA progression it was 0.55 (95% CI, 0.29–1.01). “It was exactly the same trend,” Fizazi said.
A grade 3 or higher adverse event (AE) was experienced by 67% of patients treated with capivasertib compared with for 40.4% of those in the placebo arm. A serious AE was experienced by 42.5% of those in the capivasertib group compared with for 26% of patients in the placebo arm. There was 36 AEs leading to death in the investigational arm compared with 26 in the placebo group.
Adverse events led to discontinuation of capivasertib or placebo for 18.3% and 4.8% of patients, respectively. For capivasertib and placebo, respectively, dose interruptions were required for 62.8% and 26.8% of patients and dose reductions were needed for 29% and 3.6% of patients. An AE led to discontinuation of abiraterone acetate for 9.5% and 5.4% of patients in the investigational and control arms, respectively.
The most common AEs in the capivasertib arm and placebo group, respectively, were diarrhea (51.9% vs 8.0%), hyperglycemia (38% vs 12.9%), rash (35.4% vs 7%), anemia (23.9% vs 12.7%), and hypokalemia (22.1% vs 12.7%). “Adverse events typical of abiraterone, such as hypertension, hypokalemia, and transaminase increase, were even between arms,” said Fizazi.
In early 2025,2 another study exploring capivasertib in prostate cancer was halted following an interim analysis that showed a potential lack of efficacy. This study, CAPItello-280 (NCT05348577), was exploring capivasertib in combination with docetaxel and ADT.
Outside of prostate cancer, capivasertib has gained FDA approval in combination with fulvestrant (Faslodex) for the treatment of patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.3
Raritan, New Jersey, October 19, 2025 – Johnson & Johnson (NYSE:JNJ) today announced 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) 2025 Congress (Oral Abstract #1327MO).1
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:
In addition to the Phase 1b/2 OrigAMI-4 study, RYBREVANT® is being studied in multiple clinical trials, including:
The legal manufacturer for RYBREVANT® is Janssen Biotech, Inc.
For more information, visit:
https://www.RYBREVANT.com.
RYBREVANT® IMPORTANT SAFETY INFORMATION10
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.
Please read full
Prescribing Information for RYBREVANT®.
Please read full
Prescribing Information for LAZCLUZE®.
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 SC amivantamab and RYBREVANT® (amivantamab-vmjw). 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 http://www.sec.gov, http://www.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.
Footnotes
*Prof. Kevin Harrington, MBBS, Ph.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.
Source: Johnson & Johnson
1 Harrington K, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer after disease progression on checkpoint inhibition and chemotherapy [ESMO abstract 1327MO]. Presented at: European Society for Medical Oncology 2025 Congress; October 19, 2025; Berlin, Germany.
2 Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. New England Journal of Medicine. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252
3 Cohen EEW, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. doi:10.1016/S0140-6736(18)31999-8
4 Fayette J, Licitra L, Harrington K, et al. INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research. 2025;31(13):2617-2627. doi:10.1158/1078-0432.CCR-25-0073
5 Tahara M, Greil R, Rischin D, et al. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study. European Journal of Cancer. 2025;221:115395. doi:10.1016/j.ejca.2025.115395
6 Zhang L, Chai AWY, Wong MCS, et al. Incidence and survival outcomes of human papillomavirus–associated head and neck cancers: A population-based study. JAMA Netw Open. 2024;7(7):e2421771. doi:10.1001/jamanetworkopen.2024.21771
7 Wise-Draper TM, Bahig H, Tonneau M, Karivedu V, Burtness B. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. American Society of Clinical Oncology Education Book. 2022;42:1-14. https://doi.org/10.1200/edbk_350442
8 Rothenberger NJ, Stabile LP. Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment. Cancers. 2017; 9(4):39. https://doi.org/10.3390/cancers9040039
9 Hartmann, S, et al. HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment. Clinical Cancer Research. 2016;22(16):4005-4013. https://doi.org/10.1158/1078-0432.CCR-16-0951
10 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
11 Harrington K, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer after disease progression on checkpoint inhibition and chemotherapy [ESMO abstract 1327MO]. Abstract presented in: European Society for Medical Oncology 2025 Congress Abstract Book, Annals of Oncology. 2025.
12 ClinicalTrials.gov. A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4). https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1. Accessed October 2025.
13 Barsouk A, et al. Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Medical Sciences. 2023;11(2):42. https://doi.org/10.3390/medsci11020042
14 Ghiani L, Chiocca S. High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. International Journal of Molecular Sciences. 2022;23(7):3483. https://doi.org/10.3390/ijms23073483
15 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed October 2025.
16 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed October 2025.
17 ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE® in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed October 2025.
18 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed October 2025.
19 ClinicalTrials.gov. A Study of LAZCLUZE® With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed October 2025.
20 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed October 2025.
21 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed October 2025.
22 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed October 2025.
23 ClinicalTrials.gov. A Study of LAZCLUZE® as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed October 2025.
24 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed October 2025.
25 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032?term=Swallowtail&intr=amivantamab&rank=1. Accessed October 2025.
26 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed October 2025.
27 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed October 2025.
28 ClinicalTrials.gov. A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (COPERNICUS). https://www.clinicaltrials.gov/study/NCT06667076?term=COPERNICUS&rank=3. Accessed October 2025.
29 ClinicalTrials.gov. Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (COCOON). https://www.clinicaltrials.gov/study/NCT06120140. Accessed October 2025.
30 ClinicalTrials.gov. A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (OrigAMI-1). https://clinicaltrials.gov/study/NCT05379595?term=NCT05379595&rank=1. Accessed October 2025.
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