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

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

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

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

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

A Study to Assess the Drug Levels of Repotrectinib in Healthy Participants and Participants With Moderate and Severe Hepatic Impairment (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion • Hepatology

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Repotrectinib in ROS1 Fusion-Positive Non- Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis (ERS 2025) - "Repotrectinib demonstrates strong clinical activity and a favorable safety profile, making it a valuable, patient-centered treatment option. These findings support its integration into treatment strategies for ROS1 fusion-positive NSCLC and highlight the need for larger, long-term studies."

Retrospective data • Review • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+ NSCLC (IASLC-WCLC 2025) - P1/2 | "50% of patients received ≥2 (range 1-4) prior ROS1 TKIs, of whom 93% had prior lorlatinib, repotrectinib, and/or taletrectinib. In this pivotal ROS1 TKI pre-treated data set, zidesamtinib demonstrated clinically meaningful activity and durability, including in patients with CNS disease and/or ROS1 G2032R-mutations, and/or in patients who had exhausted available options. Encouraging preliminary activity was also observed in TKI-naïve patients. Zidesamtinib's safety profile was consistent with its highly ROS1-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Solid Tumor • ROS1

Population-Adjusted Indirect Comparisons of Repotrectinib and Taletrectinib in ROS1+ aNSCLC [WITHDRAWN] (IASLC-WCLC 2025) - No abstract available

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

A Phase II Study of Repotrectinib in ROS1-Positive Non-Small Cell Lung Cancer Patients With Active Brain Metastasis - REPOSE (IASLC-WCLC 2025) - P1/2, P2 | "The steering committee will decide on continuation based on efficacy and safety. Trial activation is expected in April 2025 for Spain and Austria, and in June 2025 for Germany, with about 15 sites across the three countries.Clinical Trial Identification: NCT06315010Support and funding: Bristol-Myers Squibb (BMS)"

Clinical • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK1 • NTRK2 • NTRK3 • ROS1

Taletrectinib, a Next Generation Selective ROS1 Inhibitor, Exhibits a Differentiated Profile in ROS1 Fusion Models (IASLC-WCLC 2025) - P2 | "While FDA approved ROS1 inhibitors include crizotinib, entrectinib, and repotrectinib, patients are still in need of better treatment options that provide durable responses and prolonged progression-free survival (PFS), coupled with limited side effects. Conclusions : In summary, our nonclinical data demonstrate that, at clinically relevant concentrations, taletrectinib exhibits activity in ROS1 wild-type- and mutant-driven cancers, including intracranial models, while maintaining selectivity against TRKB, resulting in an overall favorable profile. An NDA, based on the results from the pivotal TRUST-I and TRUST-II studies, has been accepted with Priority Review by the U.S. FDA for the treatment of patients with advanced ROS1-positive NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • NTRK2

Real-World Insights on Treatment Patterns and Outcomes in ROS1 NSCLC: An Australian Multicenter Study (AURORA) (IASLC-WCLC 2025) - P | "Across all lines, entrectinib (35/93, 38%) and crizotinib (33/93, 35%) were frequently used, followed by lorlatinib (26/93, 28%), NVL-520 (24/93, 26%), repotrectinib (17/93, 18%). First-line ROS1 therapy demonstrated a median survival of 56 months, comparable to PROFILE 1001 (51 months) and exceeding other real-world cohorts (24 months), likely due to reflex molecular testing, targeted therapy access, and trial prioritisation. This real-world data provides valuable insights into the longitudinal patient journey, outcomes with serial therapies, and the potential impact of treatment sequencing."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ROS1

Repotrectinib in Patients With ROS1 Fusion-Positive (ROS1+) NSCLC: Long-Term Follow-Up From the Phase 1/2 TRIDENT-1 Trial (IASLC-WCLC 2025) - P1/2 | "Conclusions : Repotrectinib continued to demonstrate durable efficacy and intracranial activity in patients with ROS1 + NSCLC in the TKI-naïve and the 1 prior TKI and no chemo cohorts of TRIDENT-1, with median follow-up of ≥42 months. Safety outcomes were consistent with previous reports."

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

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial) (clinicaltrials.gov) - P2 | N=58 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial primary completion date • Oncology