Larotrectinib Sulfate

A 295,000+ patient study revealed variable efficacy among cancers for patients treated with tissue-agnostic drugs and uncovered the potential for expanding approvals to other drugs of the same class IRVING, Texas, March 20, 2025 /PRNewswire/ -- Caris Life Sciences® (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, today announced the publication of "Real-world evidence provides clinical insights into tissue-agnostic therapeutic approvals" in Nature Communications. Utilizing the largest real-world clinical and genomic dataset of tissue-agnostic indications reported to date across more than 295,000 patients, the study provides a comprehensive evaluation of real-world outcomes for patients eligible for these powerful "pan-cancer" therapies, such as pembrolizumab and larotrectinib. These drugs are categorized as tumor-agnostic therapies, targeting specific genetic or molecular features of tumors rather than their anatomical location or histology. The study focused on the use and clinical benefits of tissue-agnostic therapies, which target specific molecular biomarkers across numerous cancer types. Key findings include: More than 20 percent of patients are candidates for a tissue-agnostic drug. Approximately five percent of patients who lacked any tumor-specific indication were found to carry a tissue-agnostic indication and became eligible for tissue-agnostic drug treatment. Tissue-agnostic therapy uptake was poor for rare indications, illustrating the need for enhanced clinical education. Current tissue-agnostic indications could potentially be expanded, as evidenced by clinical benefits in tumor types and drugs of the same class that were not investigated in the original clinical trials. "By harnessing the power of Caris' large clinico-genomic dataset, we have shown that tissue-agnostic drugs produce different outcomes in different tissues," said George W. Sledge, Jr., MD, EVP and Chief Medical Officer of Caris and study author. "We additionally found evidence of clinical benefit beyond approved indications, illustrating the enormous potential of real-world data to inform the clinical use of tissue-agnostic drug approvals, potentially improving patient outcomes." "Caris has generated one of the most extensive clinico-genomic datasets in oncology through years of comprehensive molecular profiling," said Caris President and study author David Spetzler, MS, PhD, MBA. "Our advanced analyses of real-world data now enable us to uncover findings of clinical value for large patient populations. One in five patients in our study were eligible for a tissue-agnostic drug, which demonstrates the widespread impact of our findings." Detailed Scientific Information This study used a real-world database of 295,316 molecularly profiled tumor samples with associated clinical outcomes data across 57 tumor types to investigate the utility and uptake of six tissue-agnostic therapies (pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib and selpercatinib). At least one current FDA-approved tissue-agnostic indication (TMB-High, MSI-High/dMMR, BRAFV600E mutations, and NTRK and RET fusions) was detected in 21.5% of patients, including 5.4% lacking any tumor-specific indication. In patients with rare NTRK fusions, there was poor clinical uptake of the clinically successful targeted therapies larotrectinib and entrectinib, underlining the need for oncologist education on rare indications. Strikingly, significant differences in pembrolizumab-associated outcomes were observed across tumor types for the most common indications (TMB-High and MSI-High/dMMR), demonstrating that the effects of these therapies are not tissue-agnostic. Clinical benefits were also observed in tumor types and drugs of the same class (such as nivolumab) that were not investigated in pivotal clinical trials. This suggests the possible expansion of therapeutic avenues for a given tissue-agnostic indication. These findings demonstrate the power of Caris' extensive real-world dataset for generating valuable clinical insights to inform the clinical implementations of tissue-agnostic drug approvals and improve outcomes for patients with cancer. Designed to capture and analyze molecular information from tissue and blood in a comprehensive manner, the proprietary Caris Platform is a powerful set of precision medicine solutions, providing Whole Exome Sequencing (WES) and Whole Transcriptome Sequencing (WTS) as standard practice. Caris sequences at sector-leading depth of coverage, which directly correlates to increased accuracy and detection of low-frequency biomarkers of relevance. Caris also evaluates protein biomarkers through an extensive menu of immunohistochemical (IHC) tests analyzed in a tumor-type specific manner, which in combination with WES and WTS, provides a comprehensive view of a patient's disease across DNA, RNA and proteins. The Caris approach reveals an individualized molecular blueprint of a patient's disease, providing actionable, personalized treatment pathways and driving superior clinical outcomes for patients. About Caris Life Sciences Caris Life Sciences® (Caris) is a leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, multimodal database and computing capability needed to analyze and further unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides a differentiated platform to deliver the next generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Caris was founded with a vision to realize the potential of precision medicine in order to improve the human condition. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Cambridge (MA), Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S. and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media: Corporate Communications [email protected] 214.294.5606 SOURCE Caris Life Sciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

As biomarker testing and the demand for tumor-agnostic therapies rise, ROZLYTREK can potentially target a specialized yet valuable market segment. While competition from other TRK inhibitors, such as larotrectinib (VITRAKVI), may influence growth, its ability to penetrate the CNS provides a distinct advantage. LAS VEGAS, March 12, 2025 /PRNewswire/ -- DelveInsight's " ROZLYTREK Market Size, Forecast, and Market Insight Report" highlights the details around ROZLYTREK, an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1, and ALK with IC50 values of 0.1 to 2 nM. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of ROZLYTREK. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Roche's ROZLYTREK (entrectinib) Overview ROZLYTREK is a tumor-agnostic therapy that introduces a novel approach to cancer treatment. Its active ingredient, entrectinib, inhibits tropomyosin receptor tyrosine kinases (TRKA, TRKB, and TRKC), which are encoded by the NTRK1, NTRK2, and NTRK3 genes. It also targets ROS1 and ALK, with IC50 values ranging from 0.1 to 2 nM, while showing weaker inhibition of JAK2 and TNK2 (IC50 > 5 nM). The primary active metabolite, M5, exhibits similar inhibitory activity against TRK, ROS1, and ALK. Fusion proteins involving TRK, ROS1, or ALK kinase domains can promote tumor growth by excessively activating downstream signaling pathways, leading to uncontrolled cell proliferation. Entrectinib has demonstrated both in vitro and in vivo efficacy in inhibiting cancer cell lines across multiple tumor types carrying NTRK, ROS1, or ALK fusions. Additionally, it achieves steady-state brain-to-plasma concentration ratios between 0.4 and 2.2 in animal studies (mice, rats, and dogs) and has shown anti-tumor effects in mice with intracranial tumors driven by TRKA and ALK. ROZLYTREK is an orally administered, once-daily treatment approved for NTRK fusion-positive solid tumors and ROS1-positive NSCLC in several countries, including Australia, Canada, the EU, Israel, Japan, New Zealand, South Korea, Taiwan, and the US, with additional regulatory reviews ongoing worldwide. The recommended ROZLYTREK dosage for ROS1-positive NSCLC is 600 mg once daily, with or without food, until disease progression or unacceptable toxicity. For NTRK fusion-positive solid tumors, the ROZLYTREK dosage guidelines are as follows: Adults and pediatric patients with a body surface area (BSA) of ≥1.51 m²: 600 mg once daily Pediatric patients older than 6 months: 300 mg/m² to a maximum of 600 mg Pediatric patients between 1 month and 6 months: 250 mg/m² once daily Learn more about ROZLYTREK projected market size for ROS1 NSCLC @ ROZLYTREK Market Potential Receptor Tyrosine Kinase (ROS1) is an essential transmembrane receptor protein that regulates key cellular functions such as apoptosis, survival, differentiation, proliferation, migration, and transformation. It plays a pivotal role in various cancers, including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and NSCLC. A ROS1 inhibitor is a drug designed to block the activity of abnormal ROS1 fusion proteins present in certain cancer cells. By inhibiting this protein, these inhibitors help restrict cancer cell growth and metastasis. As a type of targeted therapy, ROS1 inhibitors also act on multiple kinases, including Anaplastic Lymphoma Kinase (ALK) and Mesenchymal Epithelial Transition (MET), alongside ROS1. These inhibitors specifically target the kinase domain of ROS1, with conventional kinases classified into DFG-in (active, type I) and DFG-out (inactive, type II) based on their domain structure. For patients with stage IV ROS1-positive NSCLC, treatment with a ROS1 tyrosine kinase inhibitor (TKI) is recommended. ROS1 inhibitors have demonstrated remarkable efficacy in treating NSCLC, encompassing both approved therapies and emerging treatments under development. They have significantly advanced NSCLC management, establishing themselves as a crucial therapeutic approach. The current market for ROS1-positive NSCLC is largely dominated by TKIs such as XALKORI. According to DelveInsight's analysis, the market size for ROS1 inhibitors in NSCLC across the 7MM was valued at approximately USD 290 million in 2023, with the United States contributing the largest share. The market for ROS1 inhibitors is projected to experience substantial growth in the coming years. This expansion is driven by rising biomarker testing rates, a growing number of cancer diagnoses, increased awareness of ROS1 mutations, and the introduction of next-generation ROS1 TKIs. These advanced therapies offer improved CNS penetration and a broader range of coverage against ROS1 resistance mutations compared to first-generation TKIs. Discover more about the ROS1 inhibitors market in detail @ ROS1 Inhibitors Market Report Emerging Competitors of ROZLYTREK The promising ROS1 inhibitors in the pipeline that will give tough competition to Roche's ROZLYTREK include DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Zidesamtinib (NVL-520) (Nuvalent), ANS03 (Avistone Biotechnology), Zanidatamab (Jazz Pharmaceuticals), PT-112 (Promontory Therapeutics), and others. In December 2024, Nuvation Bio announced that the US FDA had granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 2025. The company is preparing for a launch as early as mid-2025. To know more about the number of competing drugs in development, visit @ ROZLYTREK Market Positioning Compared to Other Drugs Key Milestones of ROZLYTREK In October 2023, the US FDA granted accelerated approval to ROZLYTREK in new oral pellet form for pediatric patients older than 1 month with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy. In August 2020, the EC granted conditional marketing authorization for ROZLYTREK for the treatment of adult and pediatric patients 12 years of age and older with solid tumors expressing an NTRK gene fusion, who have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options. The EC also approved ROZLYTREK for the treatment of adults with ROS1-positive, advanced NSCLC not previously treated with ROS1 inhibitors. In February 2020, Chugai obtained approval for an additional indication of ROZLYTREK for the treatment of ROS1 fusion-positive, unresectable, advanced, or metastatic NSCLC from the MHLW. In September 2019, Chugai Pharmaceutical announced the launch of ROZLYTREK 100 mg and 200 mg capsules, for the treatment of NTRK fusion-positive advanced or recurrent solid tumors. In August 2019, the US FDA approved ROZLYTREK to treat adults with ROS1-positive, metastatic NSCLC. The FDA has also granted accelerated approval to ROZLYTREK for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. In June 2019, the MHLW approved ROZLYTREK for treating adult and pediatric patients with NTRK fusion-positive, advanced recurrent solid tumors. In February 2019, the US FDA issued a priority review designation letter to ROZLYTREK adult patients with metastatic NSCLC whose tumors are ROS1–positive. In December 2018, ROZLYTREK received ODD in Japan with the intended indication of NTRK fusion-positive, locally advanced, or metastatic solid tumors. In September 2018, ROZLYTREK received SAKIGAKE designation for the treatment of adult and pediatric patients with NTRK gene fusion-positive, locally advanced, or metastatic solid tumors who have progressed following prior therapies or have no acceptable standard therapies. In July 2018, Chugai entered into a license agreement with Roche for entrectinib. Under the terms of the agreement, Chugai obtains exclusive rights for the development and marketing of entrectinib in Japan and will make upfront and milestone payments to Roche. In December 2017, Roche and Ignyta entered a definitive merger agreement for Roche to fully acquire Ignyta for USD 27.00 per share in an all-cash transaction. In October 2017, ROZLYTREK was awarded PRIME status for treating NTRK fusion-positive, locally advanced, or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapy by EMA. In May 2017, ROZLYTREK was granted BTD for the treatment of NTRK fusion-positive, locally advanced, or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies by the US FDA. In February 2015, the US FDA granted ODD to ROZLYTREK for treating TrkA-positive, TrkB-positive, TrkC-positive, ROS1-positive or ALK-positive NSCLC. Discover how ROZLYTREK is shaping the ROS1 NSCLC treatment landscape @ Roche ROZLYTREK ROZLYTREK Market Dynamics ROZLYTREK competitive positioning in the market is driven by its tumor-agnostic approval, allowing it to cater to multiple rare cancers with a single therapy. The drug has gained regulatory approval in major markets, including the US, Europe, and Japan, benefiting from an increasing emphasis on biomarker-driven oncology treatments. Its key competitor, Bayer's VITRAKVI (larotrectinib), has a similar mechanism of action but differs in pharmacokinetics and tolerability, creating a nuanced competitive landscape. Market adoption of ROZLYTREK is influenced by the growing use of comprehensive genomic profiling (CGP) in oncology, which facilitates the identification of eligible patients with NTRK or ROS1 fusions. However, its commercial success is partially constrained by the rarity of these genetic alterations, which limits the addressable patient population. Additionally, the high cost of precision oncology therapies and reimbursement challenges in certain healthcare systems can impact uptake. Nonetheless, increasing awareness and advancements in diagnostic infrastructure are expected to support market growth. From a strategic perspective, Roche has leveraged partnerships and real-world evidence to expand the drug's adoption. The company is actively working on label expansions and combination strategies to maximize ROZLYTREK's commercial potential. Additionally, the growing use of next-generation sequencing (NGS) panels in routine cancer diagnostics may boost the identification rate of eligible patients, driving future market penetration. The competitive landscape could see further evolution with the potential entry of new TRK/ROS1 inhibitors, particularly next-generation agents designed to address resistance mutations. However, ROZLYTREK's strong clinical efficacy, broad tissue-agnostic approval, and Roche's global oncology expertise position it well in the precision medicine segment. As personalized oncology continues to gain traction, the drug's long-term success will depend on physician awareness, diagnostic advancements, and favorable pricing and reimbursement strategies. Dive deeper to get more insight into ROZLYTREK's strengths & weaknesses relative to competitors @ ROZLYTREK Market Drug Report Table of Contents Related Reports ROS1 Inhibitors Market ROS-1 Inhibitors Market Size, Target Population, Competitive Landscape & Market Forecast – 2034 report deliver an in-depth understanding of the market trends, market drivers, market barriers, and key ROS1 inhibitors companies, including AnHeart Therapeutics, Nuvalent, Bristol Myers Squibb, Genentech, Pfizer, among others. Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED