Cellares and University of Wisconsin School of Medicine and Public Health Expand Partnership to Clinical Manufacturing of CRISPR-Edited CAR-T for Solid Tumors

On February 18, 2026 Cellares, the first Integrated Development and Manufacturing Organization (IDMO), and the University of Wisconsin (UW) School of Medicine and Public Health reported an expansion of their partnership to support clinical production and regulatory advancement of the university’s CRISPR-edited GD2 CAR-T investigational therapy for pediatric and adult solid tumors.

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The collaboration builds on the initial partnership announced in April 2025, which focused on automating the university’s internally developed CAR-T process. Based on the strong performance and reliability demonstrated in automated manufacturing, the university selected Cellares to support the program’s transition to clinical manufacturing.

Cellares will provide manufacturing support using its Cell Shuttle end-to-end automated platform and Cell Q automated quality control platform. Cellares will also provide regulatory expertise to support the preparation and submission of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA), including contributions to the Chemistry, Manufacturing and Controls (CMC) section. The university retains full ownership and leadership of the IND filing process.

The GD2 CAR-T program targets solid tumors in pediatric and adult patients, initially focusing on high-grade gliomas, and could inform future studies in neuroblastoma, osteosarcoma, and melanoma, which are GD2+ cancers with limited therapeutic options in the refractory or relapsed setting. The program uses CRISPR gene editing to modify patient T cells via electroporation, an approach that requires precise, reproducible manufacturing to ensure each batch meets specifications. The Cell Shuttle’s end-to-end automation reduces manual handling and process variability. Addressing these factors can help support advancing cell therapies to clinical trials.

"Outcomes of our initial collaborative work with Cellares met the specified performance standards. We are focused on next steps for bringing this from bench to bedside," said Christian Capitini, M.D., Professor of Pediatrics and the Jean R. Finley Professor in Pediatric Hematology and Oncology at the University of Wisconsin School of Medicine and Public Health.

"Academic medical centers originate many of the cell therapies that eventually reach patients, but the path from proof-of-concept to IND-ready production has historically added years to the development timeline," said Fabian Gerlinghaus, Co-founder and Chief Executive Officer of Cellares. "We believe that automated production can shorten that path and, through this clinical manufacturing collaboration with UW, we are committed to applying the Cell Shuttle and Cell Q platforms to support the full development lifecycle."

(Press release, University of Wisconsin, FEB 18, 2026, View Source [SID1234662769])

Flatiron Launches First-of-Its-Kind AI-Powered Global Prostate Cancer Datasets

On February 18, 2026 Flatiron Health, a leading healthtech company dedicated to improving cancer care and advancing research using real-world data, reported their first Panoramic datasets in the UK and Germany for patients with prostate cancer. Globally, prostate cancer affects nearly 1.5 million patients annually and has a rapidly evolving treatment landscape, yet real-world evidence remains limited and infeasible to study across international borders.

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Flatiron is the first and only company to deliver global real-world data in this key oncology indication, leveraging proprietary AI and large language model capabilities to build on their Global Evidence Platform. The prostate cancer Panoramic datasets, which encompass the records of nearly 400,000 patients, unlock high-quality, source-level unstructured and structured EHR data across Germany, the UK, and the US. Built on a common data model across all regions, these datasets enable unprecedented interoperability—allowing researchers to seamlessly analyze patient outcomes and treatment patterns across markets to inform global evidence strategies.

"Flatiron is not just adding more data; we are building the singular destination for global oncology intelligence." said Kate Estep, Chief Product Officer at Flatiron Health. "By unifying fragmented global records into a single evidence platform, we are fundamentally changing how our customers develop therapies and—most importantly—when patients can access them."

This launch delivers immediate value to Flatiron’s life science customers. The prostate Panoramic dataset builds on already available offerings to create a full scope of understanding for genitourinary cancers, specifically:

The rich data provides all Prostate-Specific Membrane Antigen (PSMA) PET scan data, all prostate-specific antigen (PSA) values across the patient journey, and 19 Homologous Recombination Repair (HRR) genes, plus recurrence and progression details, enabling answers to key questions like how novel therapies are being used and which patients are benefiting most.
Proprietary AI and large language model capabilities that unlock the full scale of the company’s network, with continuous recency to reflect the evolving treatment landscape and capture newly approved treatments as they enter the market.
Unique patient-level EHR data captured through established site partnerships across Germany, the UK, and the US enable multiregional insights spanning early to late-stage disease and variations across markets.
All Flatiron datasets are validated against the company’s rigorous quality standards, reflect real-world clinical practice, and built by expert teams local to each geography, equipping researchers with the depth needed to answer oncology’s most pressing questions. Combined with the company’s bladder Panoramic dataset—now spanning the full disease spectrum from early-stage through advanced and metastatic disease—these offerings are a clear answer to persistent evidence gaps across genitourinary cancers.

"The field of prostate cancer is evolving at a rapid pace, changing how care is sequenced from early-stage disease through metastatic CRPC and improving outcomes for patients. Yet critical evidence gaps remain, as we see significant regional variation in how novel therapies are used, and in how uneven access to advanced diagnostics differentially influences treatment decisions," said Emily Castellanos, MD, MPH, Senior Medical Director and Head of Research Oncology at Flatiron Health. "From a clinical perspective, Flatiron’s global Panoramic datasets directly address these evidence gaps, enabling life science companies to increase confidence in decision-making earlier and accelerate development timelines across diseases and geographies, thereby bringing the next generation of precision medicine to all patients sooner."

This launch marks the first in a series of global dataset expansions, with longitudinal breast cancer and non-small cell lung cancer (NSCLC) datasets planned for 2027. These expansions reinforce Flatiron Health as the gold standard in oncology data, intelligence, and technology. For over a decade, Flatiron has powered the highest-stakes decisions in cancer care and drug development with insights the industry did not have before—shaping what regulators, researchers, clinicians, and biopharma expect from oncology evidence and continuing to redefine that standard. By integrating rigorous real-world data with AI-driven intelligence, Flatiron is doing more than delivering datasets, it is transforming real-world patient experiences into decision-shaping insights that define the future of global cancer care.

(Press release, Flatiron Health, FEB 18, 2026, View Source [SID1234662768])

CEL-SCI Reports Fiscal First Quarter 2026 Results

On February 18, 2026 CEL-SCI Corporation (NYSE American: CVM) reported financial results for three months ended December 31, 2025, as well as key recent clinical and corporate developments.

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"CEL-SCI is focused on two major value-driving milestones in the near term—starting enrollment in our U.S. FDA confirmatory Registration trial of Multikine in head and neck cancer and advancing Multikine globally in markets including Saudi Arabia. We plan to commence enrollment this summer in our confirmatory study of Multikine in head and neck cancer. Data from this study will be submitted as part of registration applications to allow commercialization and sale of Multikine in the U.S. and other key global markets. Prior studies have shown that pre-surgical tumor responses, such as tumor size reduction and downgrading of the disease by a physician, following Multikine treatment predict substantial survival benefit for the patients. We believe that these pre-surgical tumor responses after the three-week treatment with Multikine, before any other treatment has been administered, could be the basis of an accelerated marketing application for Multikine," stated CEL-SCI CEO, Geert Kersten. "Concurrently, we have been active in Saudi Arabia, pursuing the potential for Multikine to be available to patients with head and neck cancer following the filing for Breakthrough Medicine Designation there in the second half of 2025."

Clinical and Corporate Developments:

CEL-SCI, in conjunction with its CRO Ergomed, expects to start patient enrollment in the summer of 2026 for the 212-patient U.S. Confirmatory Registration Study for Multikine (Leukocyte Interleukin, Injection)* in newly diagnosed locally advanced head and neck cancer patients. Pre-surgical tumor responses, following a very short treatment with Multikine, can be assessed within weeks after full enrollment for rapid confirmation of Multikine’s anti-tumor activity, creating the potential for early accelerated approval in the U.S. CEL-SCI plans to seek accelerated approval based on early tumor response data. Ergomed is providing comprehensive global clinical operations support to ensure the timely and efficient execution of the trial. CEL-SCI and Ergomed are building on their previous successful collaboration for the global Phase 3 trial of Multikine, the largest study ever conducted in head and neck cancer. In the Phase 3 study, Multikine treatment, given right after diagnosis and before any other treatment, significantly increased the 5-year overall survival rate of the treated patient population to 73% vs 45% in patients treated with standard of care alone and halved the risk of death from 55% to 27%.
CEL-SCI is actively engaged with potential partners and investors in Saudi Arabia to advance Multikine to market. A Breakthrough Medicine Designation application for Multikine for the treatment of head and neck cancer was submitted to the Saudi Food and Drug Authority (SFDA). The designation, if granted, will allow patient access to Multikine for the indication, as well as reimbursement/sale in Saudi Arabia.
Financial Results

During the three months ended December 31, 2025, research and development expenses were $3.7 million compared to $4.4 million for the three months ended December 31, 2024. General and administrative expenses for the three months ended December 31, 2025 were $1.7 million compared to $2.5 million for the three months ended December 31, 2024. Net loss was $5.5 million for three months ended December 31, 2025 compared to $7.1 million in the prior year period. Cash used for operating activities during the quarter was $4.0 million. Basic and diluted net loss per common share was $0.68 for the three months ended December 31, 2025, compared to $3.25 for the three months ended December 31, 2024.

(Press release, Cel-Sci, FEB 18, 2026, View Source [SID1234662767])

Ankyra Therapeutics Presents First Preclinical Data on ANK-203, a Novel CD137-Anchored Immunotherapy Candidate, in Oral Session at AACR IO

On February 18, 2026 Ankyra Therapeutics, a clinical-stage biotechnology company pioneering anchored immunotherapy to deliver better outcomes for people with cancer and other serious diseases, reported preclinical data on ANK-203, a first-in-class anchored immunotherapy using monoclonal antibody CD137 (4-1BB). The data were presented today in an oral session, "Agonistic CD137 (4-1BB) anchored immunotherapy (ANK-203) elicits potent 4-1BBL signaling in vitro and therapeutic responses against established tumors without systemic toxicity in vivo" (abstract # 64034) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology Conference in Los Angeles, CA.

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"Our anchored immunotherapy platform has already demonstrated promising clinical activity with tolododekin alfa, validating our approach to improving the therapeutic index of potent immune modulators, like IL-12," said Howard Kaufman, MD, and Chief Executive Officer at Ankyra Therapeutics. "ANK-203 extends our platform’s application beyond cytokines to monoclonal antibodies and expands our pipeline, reinforcing its versatility and underscoring the potential to realize the promise of therapeutics that have been shelved due to toxicity."

ANK-203 is designed to activate the CD137 (4-1BB) immune pathway through localized delivery and retention at the tumor site. In preclinical studies, ANK-203 demonstrated robust activation of the CD137 (4-1BB) immune pathway and regression of established tumors following localized administration. Treatment was well tolerated, with no significant safety signals observed. In addition to local tumor control, ANK-203 induced anti-tumor responses in distant, untreated tumors, suggesting the induction of a systemic immune response.

"CD137 has long been recognized as a powerful immune costimulatory molecule with a high potential for cancer immunotherapy, but safety challenges have constrained its clinical potential," said Sailaja Battula, PhD, Chief Scientific Officer at Ankyra Therapeutics. "By anchoring CD137 locally, ANK-203 enables focused immune activation where it matters most – at the tumor site – while minimizing systemic exposure, offering a differentiated approach to maximize clinical benefit."

Based on these findings, Ankyra plans to advance ANK-203 through additional preclinical studies to further characterize immune mechanisms and support potential clinical development.

(Press release, Ankyra Therapeutics, FEB 18, 2026, View Source [SID1234662766])

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) receives U.S. FDA Breakthrough Therapy Designation for patients with advanced head and neck cancer

On February 18, 2026 Johnson & Johnson (NYSE: JNJ) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for subcutaneous amivantamab and hyaluronidase-lpuj as a monotherapy for the treatment of adults with head and neck squamous cell carcinoma that is recurrent or metastatic and human papillomavirus (HPV)-unrelated after disease progression on or after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. RYBREVANT FASPRO is approved in multiple settings for the treatment of locally advanced or metastatic non-small cell lung cancer and is also being evaluated in additional solid tumors, including colorectal cancer.

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HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma is characterized by high rates of epidermal growth factor receptor (EGFR) expression and mesenchymal-epithelial transition (MET) pathway overexpression.1,2,3 Subcutaneous amivantamab is designed to target both pathways, while activating the immune system. The clinical activity observed to date supports further evaluation in this setting, where treatment options remain limited after prior lines of therapy.4

"Patients with HPV-unrelated recurrent or metastatic head and neck cancer often face rapid disease progression and have limited treatment options," said Kiran Patel, Vice President, Global Head, Solid Tumor Clinical Development and Diagnostics, Johnson & Johnson. "Receiving Breakthrough Therapy Designation underscores the FDA’s recognition of these early clinical data and the urgent need for new therapies. Dual targeting EGFR and MET has shown meaningful clinical benefit in lung cancer, helping patients live longer by changing disease biology and preventing treatment resistance. We are now applying this same multi-targeted approach in head and neck cancer with the goal of improving outcomes for patients."

The BTD is supported by data from the open–label Phase 1b/2 OrigAMI–4 study. Results were presented in a mini-oral session at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and demonstrate promising clinical activity, with rapid and durable responses, in a heavily pretreated patient population.5 Based on these findings, subcutaneous amivantamab is being further evaluated in the ongoing Phase 3 OrigAMI-5 study (NCT07276399), which is assessing the subcutaneous formulation of amivantamab in combination with pembrolizumab and carboplatin versus 5-fluorouracil (5FU) plus pembrolizumab and platinum-based chemotherapy (cisplatin or carboplatin) as a first-line treatment in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma, regardless of PD-L1 expression.6

The FDA grants BTD to expedite the development and regulatory review of investigational medicines intended to treat serious or life-threatening conditions, where preliminary clinical evidence indicates the therapy may demonstrate substantial improvement over available treatment options on at least one clinically meaningful endpoint.7

About the OrigAMI-4 Study

OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study evaluating RYBREVANT FASPRO in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes five cohorts, including Cohort 1, which studied RYBREVANT FASPRO 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. RYBREVANT FASPRO 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**.8

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.9 It develops in the mucosal linings of the oral cavity, oropharynx, hypopharynx, and larynx.9 Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).9 Around 75 percent of cases are HPV-negative, which is typically associated with a poorer prognosis and reduced response to treatment.9,10 Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.1,4

About RYBREVANT FASPRO and RYBREVANT

In December 2025, the U.S. FDA approved RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) across all indications of intravenous RYBREVANT (amivantamab-vmjw). This subcutaneously administered therapy is also approved in Europe, Japan, China, and other markets.

RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

The effectiveness of RYBREVANT FASPRO has been established based on adequate and well-controlled studies of RYBREVANT. Data across multiple Phase 3 studies, including MARIPOSA, have demonstrated the clinical benefit of RYBREVANT in improving progression-free survival (PFS) and overall survival (OS) in advanced EGFR-mutated non-small cell lung cancer (NSCLC).

RYBREVANT is approved in the U.S., Europe and other markets across four indications in EGFR-mutated NSCLC, including two in the first-line setting and two in the second line, for patients with either exon 19 deletions, exon 21 L858R mutations, or exon 20 insertion mutations, as monotherapy or in combination with LAZCLUZE (lazertinib) or chemotherapy.

RYBREVANT is a first-in-class, fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines)§11 include amivantamab-vmjw (RYBREVANT) across multiple treatment settings, including its recent inclusion as a NCCN Category 1 preferred option when used with lazertinib (LAZCLUZE) for first-line treatment of people with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Amivantamab and hyaluronidase-lpuj subcutaneous injection (RYBREVANT FASPRO) may be substituted for IV amivantamab-vmjw (RYBREVANT). See the latest NCCN Guidelines for NSCLC for complete information.†‡

The NCCN Guidelines for Central Nervous System Cancers also identify amivantamab-vmjw (RYBREVANT)-based regimens, including the combination with lazertinib (LAZCLUZE), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases.†‡

The legal manufacturer for RYBREVANT is Janssen Biotech, Inc. For more information, visit: View Source

INDICATIONS

RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) and RYBREVANT (amivantamab-vmjw) are indicated:

in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.

in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.

as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION FOR RYBREVANT FASPRO AND RYBREVANT12,13,14

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

Hypersensitivity and Administration-Related Reactions with RYBREVANT FASPRO

RYBREVANT FASPRO can cause hypersensitivity and administration-related reactions (ARRs); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours.

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3 (n=206), all Grade ARRs occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARRs, 89% occurred with the initial dose (Week 1, Day 1).

Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT FASPRO as recommended. Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO injection if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO based on severity.

Infusion-Related Reactions with RYBREVANT

RYBREVANT can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT with LAZCLUZE

In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT in 4.5% of patients.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population (n=281), IRRs occurred in 50% of patients including Grade 3 (3.2%) adverse reactions. IRR-related infusion modifications occurred in 46%, and permanent discontinuation of RYBREVANT in 2.8% of patients.

RYBREVANT as a Single Agent

In CHRYSALIS (n=302), IRRs occurred in 66% of patients. IRRs occurred in 65% of patients on Week 1 Day 1, 3.4% on Day 2 infusion, 0.4% with Week 2 infusion, and were cumulatively 1.1% with subsequent infusions. 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range: 0.1 to 18 hours) after start of infusion. IRR-related infusion modifications occurred in 62%, and permanent discontinuation of RYBREVANT in 1.3% of patients.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of IRRs. Monitor patients for signs and symptoms of IRRs in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT.

Interstitial Lung Disease/Pneumonitis

RYBREVANT FASPRO and RYBREVANT can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3, ILD/pneumonitis occurred in 6% of patients, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9% of patients. 5% of patients permanently discontinued RYBREVANT FASPRO and LAZCLUZE due to ILD/pneumonitis.

RYBREVANT with LAZCLUZE

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT and LAZCLUZE due to ILD/pneumonitis.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% of patients with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT due to ILD/pneumonitis.

RYBREVANT as a Single Agent

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT FASPRO or RYBREVANT and LAZCLUZE (when applicable) in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Events with Concomitant Use with LAZCLUZE

RYBREVANT FASPRO and RYBREVANT in combination with LAZCLUZE can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of treatment.

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3 (n=206), all Grade VTE occurred in 11% of patients and 1.5% were Grade 3. 80% (n=164) of patients received prophylactic anticoagulation at study entry, with an all Grade VTE incidence of 7%. In patients who did not receive prophylactic anticoagulation (n=42), all Grade VTE occurred in 17% of patients. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390).

RYBREVANT with LAZCLUZE

In MARIPOSA, VTEs occurred in 36% of patients including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE; 1% of patients had VTE leading to dose reductions of RYBREVANT, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended.

Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT FASPRO or RYBREVANT and LAZCLUZE based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO or RYBREVANT and LAZCLUZE at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT FASPRO or RYBREVANT. Treatment can continue with LAZCLUZE at the same dose level at the discretion of the healthcare provider. Refer to the LAZCLUZE Prescribing Information for recommended LAZCLUZE dosage modification.

Dermatologic Adverse Reactions

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

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3, rash occurred in 80% of patients, including Grade 3 in 17% and Grade 4 in 0.5% of patients. Rash leading to dose reduction occurred in 11% of patients, and RYBREVANT FASPRO was permanently discontinued due to rash in 1.5% of patients.

RYBREVANT with LAZCLUZE

In MARIPOSA, rash occurred in 86% of patients, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT and 30% for LAZCLUZE, rash leading to dose reductions occurred in 23% of patients for RYBREVANT and 19% for LAZCLUZE, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT and 1.7% for LAZCLUZE.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, rash occurred in 82% of patients, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT and 3.1% discontinued pemetrexed.

RYBREVANT as a Single Agent

In CHRYSALIS, rash occurred in 74% of patients, including Grade 3 in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% and permanent discontinuation due to rash occurred in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%).

When initiating treatment with RYBREVANT FASPRO or RYBREVANT, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.

If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT FASPRO or RYBREVANT in combination with LAZCLUZE, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT FASPRO or RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT FASPRO or RYBREVANT based on severity.

Ocular Toxicity

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

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3, all Grade ocular toxicity occurred in 13% of patients, including 0.5% Grade 3.

RYBREVANT with LAZCLUZE

In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT and continue LAZCLUZE based on severity.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, ocular toxicity occurred in 16% of patients. All events were Grade 1 or 2.

RYBREVANT as a Single Agent

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients. All events were Grade 1-2.

Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO or RYBREVANT based on severity.

Embryo-Fetal Toxicity

Based on animal models, RYBREVANT FASPRO, RYBREVANT and LAZCLUZE can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO and RYBREVANT. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT FASPRO or RYBREVANT, and for 3 weeks after the last dose of LAZCLUZE.

ADVERSE REACTIONS

RYBREVANT FASPRO with LAZCLUZE

In PALOMA-3 (n=206), the most common adverse reactions (≥20%) were rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), diarrhea (22%), vomiting (22%), constipation (22%), decreased appetite (22%), and headache (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocyte count (6%), decreased sodium (5%), decreased potassium (5%), decreased albumin (4.9%), increased alanine aminotransferase (3.4%), decreased platelet count (2.4%), increased aspartate aminotransferase (2%), increased gamma-glutamyl transferase (2%), and decreased hemoglobin (2%).

Serious adverse reactions occurred in 33% of patients, with those occurring in ≥2% of patients including ILD/pneumonitis (6%); and pneumonia, VTE and fatigue (2.4% each). Death due to adverse reactions occurred in 5% of patients treated with RYBREVANT FASPRO, including ILD/pneumonitis (1.9%), pneumonia (1.5%), and respiratory failure and sudden death (1% each).

RYBREVANT with LAZCLUZE

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

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

RYBREVANT with Carboplatin and Pemetrexed

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

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

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

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

RYBREVANT as a Single Agent

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

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

LAZCLUZE DRUG INTERACTIONS

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

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

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

(Press release, Johnson & Johnson, FEB 18, 2026, View Source [SID1234662765])