Augtyro (repotrectinib) / ZAI Lab, BMS - LARVOL DELTA

A phase II, multi-center, open-label, single-arm study to evaluate the efficacy and Safety of lorlatinib in TKI naïve, advanced ROS1-positive non-small cell lung cancer patients with brain metastases (ESMO Asia 2025) - P2 | "While ROS1-tyrosine kinase inhibitors (TKIs) (e.g., crizotinib, entrectinib, repotrectinib) improve outcomes in ROS1-positive NSCLC, intracranial efficacy remains suboptimal, representing a critical unmet need. At present, no efficacy or safety results are available. Data collection for safety and efficacy endpoints is ongoing."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

KRAS-Wild Pancreatic Cancer-More Targets than Treatment Possibilities? (PubMed, Cancers (Basel)) - "Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • FGFR • KRAS • NRG1 • NTRK • RET • ROS1

Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions. (PubMed, Oncol Res) - "The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers."

Biomarker • Journal • Pan tumor • Review • Oncology

Nociceptive sensory neuron-derived NGF orchestrates a fibrotic mesenchymal stromal cell neurogenic niche to drive tendon pathological fibrosis. (PubMed, Nat Commun) - "Therapeutically, local administration of TPX-0005 (also known as repotrectinib), a clinically used TrkA inhibitor, partially reverses excessive fibrosis and improves long-term healing outcomes. Our findings reveal a previously unrecognized neurogenic axis, highlighting the functional specificity of nociceptive sensory neuron-derived NGF in peripheral tissue repair and emphasizing the regulation of MSC neurogenic niche as a promising strategy for fibrosis prevention and treatment."

Journal • Fibrosis • Immunology • HIF1A

Evolving Therapeutic Landscape of ROS1-Positive Non-Small Cell Lung Cancer: An Updated Review. (PubMed, Curr Oncol) - "Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Rare but not forgotten: Therapeutic advancements for rare childhood cancers. (PubMed, Mol Ther Oncol) - "This includes work that led to the FDA approvals of immune checkpoint inhibitors in multiple rare pediatric tumor types, the NTRK inhibitors larotrectinib, entrectinib, and repotrectinib for children and adults with solid tumors with NTRK fusions, the ALK inhibitor crizotinib in children and adults with ALK-positive inflammatory myofibroblastic tumors, and the radioligand LUATHERA for adolescents and adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Despite these advances, the study of rare pediatric cancers faces multiple challenges including a limited number of patients for efficient and well-powered clinical trials and a dearth of financial incentives. Ongoing, coordinated efforts are needed to continue the advancement of novel treatments and improve survival and minimize late effects."

Journal • Review • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pediatrics • Sarcoma • Solid Tumor • NTRK • SSTR

Lorlatinib in Tyrosine Kinase Inhibitor-Naive Advanced ROS1-Positive Non-Small Cell Lung Cancer: A Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154."

Clinical • Journal • P2 data • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3) (clinicaltrials.gov) - P3 | N=190 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Mar 2027 ➔ Mar 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Chugai Pharmaceutical Co., Ltd…announced that it has obtained approval from the Ministry of Health, Labour and Welfare (MHLW) on October 3, 2025 for FoundationOne CDx Cancer Genomic Profile to be used as a companion diagnostic for Augtyro (repotrectinib), an anti-cancer agent/tyrosine kinase inhibitor for NTRK fusion-positive solid-tumors. (Chugai Press Release) - "Bristol-Myers Squibb K.K. obtained a partial change approval for the manufacturing and marketing authorization of Augtyro in Japan....The efficacy and safety of repotrectinib for NTRK fusion-positive advanced or recurrent solid-tumors were evaluated in the international Phase I/II clinical study (TRIDENT-1) and overseas Phase I/II pediatric clinical study (CARE)."

Diagnostic • Japan approval • Solid Tumor

Augtyro: Newly added patents in Orange Book (Orange Book) - Expiry on Jan 23, 2035

Patent • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Launch Price Dynamics of Targeted Therapies in NSCLC: Dissecting the Cost and Value Across Biomarker Segments (ISPOR-EU 2025) - "The variation was evident even within mutation types highlighting potential discrepancies in value (e.g., ROS1: $7,760 [taletrectinib] to $9,693 [repotrectinib] to $13,019 [entrectinib]; RET: $11,393 [selpercatinib] to $15,859[pralsetinib]). Despite relatively consistent monthly costs, cost per mPFS month varies significantly within mutation groups. First-line therapies demonstrate superior value, supporting early biomarker testing. Emerging targeted therapies show potential for further improving value propositions through enhanced clinical outcomes."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • KRAS • ROS1

Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology. (PubMed, Ann Med Surg (Lond)) - "Several ALK inhibitors, like crizotinib, ceritinib, lorlatinib, repotrectinib, and alectinib, have shown different levels of success, but resistance to these treatments is still a big challenge. While ALK inhibitors have shown promise, resistance mechanisms necessitate the development of combination therapies and next-generation inhibitors. Future research should focus on optimizing targeted treatment strategies to improve survival outcomes in pediatric patients with ALK-positive neuroblastoma."

Journal • Review • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • ALK

Anticipated Major Milestones in the Fourth Quarter of 2025 and Full Year 2026:…Upcoming Potential NMPA Approvals (Businesswire) - "(i) Tisotumab Vedotin (Tissue Factor ADC) in recurrent or metastatic cervical cancer following progression on or after chemotherapy; (ii) Repotrectinib (ROS1/TRK) in NTRK+ solid tumors."

China approval • Cervical Cancer

Zai Lab Announces Fourth Quarter and Full Year 2024 Financial Results and Recent Corporate Updates (Businesswire) - "Tisotumab Vedotin (Tissue Factor ADC): BLA submission in recurrent or metastatic cervical cancer following progression on or after chemotherapy in the first quarter of 2025. Bemarituzumab (FGFR2b): BLA submission in first-line gastric cancer in the first half of 2025. Repotrectinib (ROS1/TRK): supplementary NDA submission in NTRK+ solid tumors in the first half of 2025. Tumor Treating Fields (TTFields): Marketing Authorization Application submissions in second-line+ NSCLC following progression on or after platinum-based chemotherapy and in first-line pancreatic cancer...Second-Line+ Extensive-Stage SCLC (ES-SCLC): Zai Lab to present updated data at a major medical conference in the first half of 2025. Zai Lab plans to initiate a pivotal study in 2025...Other neuroendocrine tumors: Zai Lab to initiate a global Phase 1 study in the first half of 2025...ZL-6201 (LRRC15 ADC): Zai Lab to provide preclinical data update and initiate a global Phase 1 study in sarcoma."

China filing • Clinical data • New P1 trial • Preclinical • Cervical Cancer • Gastric Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor

Zai Lab Announces Second Quarter 2025 Financial Results and Recent Corporate Updates (Businesswire) - "Upcoming Potential NMPA Submissions: Bemarituzumab (FGFR2b) in first-line gastric cancer in the second half of 2025. Upcoming Potential NMPA Approvals: Tisotumab Vedotin (Tissue Factor ADC) in recurrent or metastatic cervical cancer following progression on or after chemotherapy; Repotrectinib (ROS1/TRK) in NTRK+ solid tumors."

China approval • China filing • Cervical Cancer • Gastric Cancer • Solid Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), NCCN Guidelines Navigator, the NCCN Drugs & Biologics Compendium (NCCN Compendium), the NCCN Radiation Therapy Compendium, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Non-Small Cell Lung Cancer, Version 1.2026. (NCCN)

NCCN guideline • Non Small Cell Lung Cancer

Study to Evaluate the Effect of Repotrectinib on the Drug Levels of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

REAL WORLD DATA: NEXT GENERATION SEQUENCING ANALYSES FOR PEDIATRIC BRAIN TUMORS AND ACCESS TO TARGETED THERAPY IN AN UPPER-MIDDLE-INCOME COUNTRY (SIOP 2025) - "Five patients with LGG, three with HGG and BRAFV600E mutations received dabrafenib and trametinib...One HGG patient with CDK4 amplification received palbociclib. Three patients with infant-type gliomas and ALK/ROS/NTRK fusions received lolartinib/repotrectinib... Despite molecular analysis being feasible in 31.6% of cases, targeted therapy was available to a small proportion of patients (2.8%), primarily through compassionate use. This highlights that, despite governmental and non-governmental support, access to molecular diagnostics and targeted therapies remain challenging in less privileged countries."

Biomarker • Clinical • Next-generation sequencing • Real-world • Real-world evidence • Brain Cancer • Chordoma • CNS Tumor • Ependymoma • Germ Cell Tumors • Glioma • High Grade Glioma • Medulloblastoma • Meningioma • Oncology • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • ALK • BRAF • CDK4 • KIAA1549 • NTRK • TP53

Pivotal ARROS-1 efficacy and safety data: zidesamtinib in TKI pre-treated patients with advanced/metastatic ROS1+ NSCLC (JADPRO 2025) - "BACKGROUND • Zidesamtinib is an investigational ROS1 TKI designed to be highly selective, have activity against diverse ROS1 fusions and ROS1 resistance mutations, be brain-penetrant, and avoid TRK inhibition • ARROS-1 is a global, single-arm, first-in-human Phase 1/2 clinical trial of zidesamtinib in advanced ROS1-positive (ROS1+) NSCLC and other solid tumors • Pivotal data for TKI pre-treated ROS1+ NSCLC and preliminary data for TKI-naïve ROS1+ NSCLC are presented ARROS-1 STUDY DESIGN & POPULATIONS • As of the data cut-off date of March 21, 2023, 514 patients with any ROS1+ solid tumor had been enrolled across Phase 1 and 2 – The safety population included 432 patients with advanced ROS1+ NSCLC who received zidesamtinib 100 mg QD – The efficacy population included 117 ROS1 TKI pre-treated patients with measurable disease by BICR and ≥ 6 months duration of response follow-up – The TKI-naïve cohort included 35 patients with measurable disease by BICR..."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ROS1

Reporos trial-GFPC 04-2023: Open-label phase II efficacy study of repotrectinib in frail patients with ROS1-rearranged metastatic NSCLC (ESMO 2025) - P2 | "Background ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. As of April 15, 2025, 7 patients have been included in the study. This trial receives financial support and drug supply (REPROTECTINIB) from BMS, which is not involved in the design and conduct of the study, nor in the collection, management, analysis, or interpretation of the data."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

Repotrectinib in Patients With ROS1 Fusion–Positive (ROS1+) NSCLC: Long-Term Follow-Up From the Phase 1/2 TRIDENT-1 Trial (JADPRO 2025) - "Further evaluation and targeted interventions are neededIndustry standards have changed regarding who is considered a survivor. Staff education is needed to align"

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ROS1

Repotrectinib in adult and pediatric patients with NTRK+ advanced solid tumors: Updated results from the TRIDENT-1 and CARE trials (ESMO 2025) - P1/2 | "Conclusions With longer follow-up in the TRIDENT-1 and CARE trials, repotrectinib continued to demonstrate durable efficacy in both adult and pediatric pts with NTRK + solid tumors. The safety profile was consistent with prior reports."

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

Real-world treatment patterns and outcomes in US patients (pts) with neurotrophic tyrosine receptor kinase-positive (NTRK+) solid tumors (ESMO 2025) - "rw overall survival (rwOS) and progression-free survival (rwPFS) were estimated with Kaplan-Meier methods from the start of LOT (index date), from 1L for TRKi naive or post-TRKi among pretreated (larotrectinib, entrectinib, repotrectinib). TRKi use was uncommon and predominantly in late-line settings, which may be related to timing of testing and TRKi approvals and availability of alternative therapies. More than half of TRKi- and 1L-treated pts received additional therapy, with poor outcomes, thus highlighting an unmet need after progression on initial therapy."

Clinical • HEOR • Real-world • Real-world evidence • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK

DYSPNEA IN THE SECOND TRIMESTER OF PREGNANCY: A RARE CASE OF NEW-ONSET STAGE IV LUNG ADENOCARCINOMA (CHEST 2025) - "After a 3-week hospitalization, her pleural effusion was drained, and she was discharged on Lovenox.Upon arrival to the hospital in United States, her chest X-ray revealed recurrence of moderate left-sided pleural effusion...Once extubated, she was initiated on Repotrectinib therapy and continued with outpatient management... Diagnosing lung cancer in pregnant women presents considerable physical and psychological challenges. As more cases are reported, the accumulation of data will aid in improving future management and support for similar cases."

Clinical • IO biomarker • Metastases • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Obstetrics • Oncology • Pneumonia • Pulmonary Disease • Pulmonary Embolism • Rare Diseases • Solid Tumor • Tuberculosis • EGFR • NOTCH1 • PD-L1 • ROS1

The Utility of Tissue-Agnostic Drugs in Lung Cancer Treatment. (PubMed, Pharmaceut Med) - "Current evidence suggests that these therapies show promise in treating NTRK gene fusions (larotrectinib, entrectinib, repotrectinib), BRAF V600E mutation (dabrafenib and trametinib), and RET fusions (selpercatinib) in lung cancer. However, available data are limited by small sample sizes (ranging from 4 to 247 participants per trial-cohort) and the absence of control groups. Larger, controlled studies and real-world evaluations are needed to confirm these findings and inform broader clinical use."

Journal • Pan tumor • Review • Lung Cancer • Oncology • Solid Tumor • BRAF • NTRK • RET