Rozlytrek (entrectinib) / Roche, Nerviano Medical Sciences - LARVOL DELTA

STARTRK-NG: Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (clinicaltrials.gov) - P1/2 | N=69 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor

Neurotrophin signaling in synovial fibroblasts sustains pathological vascular maturation in rheumatoid arthritis (ACR Convergence 2026) - "Fibroblast-derived neurotrophin signaling is a critical driver of pathologic vascular maturation in RA and represents a previously unrecognized mechanism contributing to persistent synovial remodeling. Our findings suggest that fibroblast-derived neurotrophin signaling is a critical pathway in sustaining mature blood vessels in RA synovia, and that neurotrophin inhibitors reverse abnormal vascular maturation in RA."

Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • ACTA2 • CD31 • NGF • NGFR • NOTCH3 • NTF3 • NTRK2 • PECAM1 • RGS5

NTRK-fused gliomas inadults:clinical, radiological andhistomolecularfeatures (EANO 2026) - "Adult NTRK-fused glial and glioneuronal tumors represent a rare and heterogeneous subgroup of tumors with responses to TRK inhibitors observed in nearly 50% of cases. Therefore, testing for NTRK fusion may provide additional therapeutic options for patients with glial and glioneuronal tumors and should be considered in younger patients and in tumors with unusual histology and/or unexpectedly aggressive behavior."

Clinical • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Glioneuronal Tumor • High Grade Glioma • Low Grade Glioma • Oncology • Pleomorphic Xanthoastrocytoma • Solid Tumor • CDKN2A • CDKN2B • IDH1 • NTRK • NTRK1 • NTRK2 • NTRK3 • PTEN • TERT • TFG • TP53

NAUTIKA1: Pathological Response and Safety of Neoadjuvant Entrectinib or Atezolizumab + Radiation in Biomarker-Selected NSCLC (IASLC-WCLC 2026) - P2 | "Conclusions : Entrectinib ( ROS1 + or NTRK +) and atezolizumab plus low-dose SBRT (PD-L1+) may be feasible as neoadjuvant therapies, with atezolizumab plus low-dose SBRT demonstrating encouraging efficacy and tolerable safety. However, the data should be interpreted with caution due to small sample sizes."

Biomarker • Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • NTRK • PD-L1 • ROS1

Cell-to-Cell Communication Analysis Reveals TRK-Cas a Novel Therapeutic Vulnerability in Sonic Hedgehog Medulloblastoma (EANO 2026) - "Together, these results indicate that TRK-C plays a crucial role in CCC by maintaining the stem-like cell population in SHH-MB. Targeting TRK-C therefore represents a promising therapeutic opportunity in preclinical models and a readily translatable treatment strategy, as entrectinib is already approved for clinical use in pediatric patients.Support/Disclosure: This research was funded in part by the Austrian Science Fund (FWF) ESP278. L."

Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • NTRK3 • SHH

Impact of Neoadjuvant TKI Therapy on Tumor Reduction and Resectability in Locally Advanced Thyroid Carcinoma (ETA 2026) - "Therapies included selective (dabrafenib/trametinib, entrectinib, larotrectinib, selpercatinib) and multikinase inhibitors (lenvatinib, cabozantinib, vandetanib)... Neoadjuvant TKI therapy demonstrated promising results in locally advanced thyroid carcinoma, achieving high disease control rates and enabling surgical resection in over one-third of cases. Outcomes were comparable between selective and multikinase TKIs, and meaningful responses were observed across histological subtypes, although survival remained significantly longer in differentiated tumors. These findings, representing one of the largest single-center cohorts, reinforce the growing role of neoadjuvant therapy in multidisciplinary management of advanced thyroid cancer."

Clinical • Metastases • Oncology • Solid Tumor • Thyroid Gland Carcinoma

How to manage radioiodine-refractory thyroid cancer in the era of precision medicine. (PubMed, Drugs Context) - "Three multi-kinase inhibitors have been approved for this indication: lenvatinib and sorafenib as a first-line option and cabozantinib as a second-line option...Thus, additional selective inhibitors have been approved: larotrectinib and entrectinib for NTRK + tumours, selpercatinib and pralsetinib for RET + tumours, and crizotinib, alectinib and lorlatinib for ALK + tumours. Such a personalized approach increases clinical benefit whilst minimizing adverse events. Future studies should focus on the combination of tyrosine kinase inhibitors and immune-checkpoint inhibitors; currently, there is no strong evidence that redifferentiation strategies add clinical benefit in terms of overall survival or progression-free survival."

Journal • Review • Oncology • Solid Tumor • Thyroid Gland Carcinoma • ALK • NTRK

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. (PubMed, Lancet Oncol) - P1, P1/2, P2 | "Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours."

Clinical • Journal • P1/2 data • Hematological Disorders • Oncology • Pediatrics • Solid Tumor

Serial Cell-Free DNA Sequencing in ROS1 Fusion-Positive Lung Cancers During Treatment With Entrectinib. (PubMed, JCO Precis Oncol) - P2 | "Serial cfDNA monitoring may complement radiographic assessments as determinants of response and resistance to entrectinib in ROS1 fusion-positive lung cancers in addition to detecting putative resistance mechanisms on progression."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ARID1A • CDH1 • NF1 • ROS1 • TP53

Tissue-Agnostic Cancer Therapy Approvals. (PubMed, Hematol Oncol Clin North Am) - "In stark contrast to conventional cancer treatments that categorize malignancies based on their tissue of origin (eg, breast, lung, renal cell, etc), tumor-agnostic therapies transcend histologic boundaries, honing in on the genetic and molecular attributes of tumors, regardless of their location. This article offers a comprehensive review of the current landscape of tissue-agnostic cancer therapies and provides clinical insights to empower surgical oncologists with a deeper understanding of these innovative therapeutic approaches."

Journal • Review • Oncology • Renal Cell Carcinoma

NTRK3 as a functional mediator of neuronal differentiation in Sonic Hedgehog pathway-activated Medulloblastoma (EANO 2026) - "Gene expression changes were evaluated by qRT-PCR using selected marker genes.Treatment of 3D tumour spheroid SHH-MB models with the TRK-C-targeting small-molecule inhibitor Entrectinib induced significant cytotoxic effects as well as structural collapse of the spheroid border in the low micromolar range...Our findings demonstrate TRK-C as a key mediator of the cellular hierarchy in SHH-MB by maintaining the NSC-like cell compartment. Targeting TRK-C represents a promising strategy for therapeutic intervention in SHH-MB."

Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • ERBB4 • NEUROD1 • NTRK3

Primary endpoint of ROSALINE: A phase II neoadjuvant study of endocrine therapy (ET) and entrectinib in invasive lobular breast carcinoma (ILBC) (ESMO-BC 2025) - P2 | "ROSALINE is the first neoadjuvant trial focused on ILBC, evaluating ET and entrectinib in HR+/HER2- disease. This investigator-initiated, single-arm, phase II trial enrolled women with stage IIA–IIIA HR+/HER2– ILBC treated with 4 cycles of letrozole (2.5 mg/day) + entrectinib (600 mg/day), + goserelin for premenopausal women, followed by surgery. The primary endpoint was not met and dose reductions were frequent. However, neoadjuvant entrectinib with ET showed activity. Correlative analyses are ongoing to clarify role of ROS1 inhibition in ILBC and identify predictive biomarkers."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDH1 • HER-2

Updated Efficacy and Safety of Taletrectinib in Patients With Advanced ROS1+ Non-Small Cell Lung Cancer (NSCLC) After Prior Entrectinib Exposure: Results From the Global TRUST-II Study (ESMO 2026) - No abstract available

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Efficacy/safety of entrectinib in patients (pts) with ROS1-positive (ROS1+) advanced/metastatic NSCLC from the Blood First Assay Screening Trial (BFAST). (ASCO 2022) - P2/3 | "These data support the clinical value of blood-based NGS as another method to inform clinical decision-making in ROS1+ NSCLC. Pts with ROS1+ NSCLC (by blood-based NGS) treated with entrectinib showed deep and durable responses, consistent with results from entrectinib trials that used tissue-based testing. No new safety signals were observed."

Clinical • Late-breaking abstract • CNS Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ROS1

MET Overexpression Is Associated With Inferior Efficacy in Advanced ROS1-Rearranged NSCLC Treated With First-Line Entrectinib (IASLC-WCLC 2026) - "Conclusions : Baseline MET overexpression was associated with inferior efficacy in advanced ROS 1-rearranged NSCLC treated with first-line entrectinib. Further investigations are warranted to elucidate the underlying mechanisms and identify potential therapeutic strategies."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ROS1

A 40-Year-Old Woman With Exertional Dyspnea and Unexplained Hypoxia. (PubMed, Chest) - "The patient received sequential ROS1-targeted therapy (crizotinib, entrectinib, repotrectinib) plus local therapies for metastatic lesions. She had no history of smoking, substance misuse, or alcohol consumption. No family history of genetic diseases was reported."

IO biomarker • Journal • Cough • Genetic Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • PD-L1 • ROS1

Distinct adverse event profiles of larotrectinib, entrectinib, and repotrectinib: a FAERS disproportionality analysis (ESMO 2026) - No abstract available

Adverse events • Oncology

Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial. (PubMed, Nat Med) - P2/3 | "The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 ."

Journal • Metastases • P2/3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast. (PubMed, Future Oncol) - P2 | "Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC."

Combination therapy • Journal • P2 data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ALK • CDH1 • ER • HER-2 • ROS1

Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER. (PubMed, PLoS One) - "Entrectinib-associated reports in NSCLC showed reproducible neurologic, cardiac, renal, and laboratory-related disproportional reporting signals across FAERS and JADER. These findings may help prioritize early safety monitoring but should be interpreted as hypothesis-generating signals rather than evidence of incidence or causality."

Adverse events • Journal • Ataxia • Cardiovascular • CNS Disorders • Cognitive Disorders • Congestive Heart Failure • Developmental Disorders • Heart Failure • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • ROS1

Updated efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic NTRK fusion-positive (fp) non-small cell lung cancer (NSCLC). (ASCO 2023) - P1, P2 | "In line with previously reported data, treatment with entrectinib was associated with deep and durable systemic and intracranial responses in pts with advanced NTRK-fp NSCLC. Clinical trial information: EUCTR 2012-000148-88, NCT02097810, NCT02568267. >"

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK

Efficacy and Safety of Taletrectinib in Patients with ROS1+ Non-Small Cell Lung Cancer: The Global TRUST-II Study (IASLC-WCLC 2024) - P2 | "In TKI-pretreated patients, 82% received prior crizotinib and 18% received prior entrectinib. With increased enrollment and longer follow-up in a geographically diverse population, taletrectinib continues to demonstrate high and durable overall responses, robust IC activity, and a favorable safety profile with low incidence of neurologic AEs in TKI-naive and TKI-pretreated patients with ROS1+ NSCLC. The efficacy and safety of taletrectinib in TRUST-II remains highly consistent with TRUST-I."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Improving public cancer care by implementing precision medicine in Norway (clinicaltrialsregister.eu) - P1/2 | N=1000 | Recruiting | Sponsor: Oslo University Hospital HF | N=6000 ➔ 1000

Enrollment change • Oncology

Age-stratified adverse-event reporting signals of seven ALK/ROS1 tyrosine kinase inhibitors in FAERS: a disproportionality and time to onset study. (PubMed, Front Pharmacol) - "The study included 38,479 primary-suspect reports with known age for crizotinib, entrectinib, brigatinib, lorlatinib, repotrectinib, cabozantinib, or ceritinib...The early reporting pattern favors close assessment soon after treatment initiation. FAERS signals remain hypothesis-generating and require confirmation in longitudinal patient-level data."

Adverse events • Journal • Oncology • Pediatrics • ALK • ROS1

Cell-type specific analyses in blood and gut identify cis-eQTL matching 140 IBD risk loci and entrectinib as repurposing candidate. (PubMed, Nat Commun) - "We uncover matching regulatory modules for 140 risk loci, implicating >300 e-genes not previously connected with inflammatory bowel disease, and find 152 matching e-genes whose expression is perturbed in the blood or gut of patients. We identify entrectinib, a small molecule inhibiting the NRLP3 inflammasome by binding NEK7, as a possible repurposing candidate."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease