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

Reporos trial-GFPC 04-2023: open-label phase II efficacy study of repotrectinib in frail patients with ROS1-rearranged metastatic NSCLC (ESMO 2025) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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) - No abstract available

Clinical • Metastases • Oncology • Solid Tumor • NTRK

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Population-Adjusted Indirect Comparisons of Repotrectinib and Taletrectinib in ROS1+ aNSCLC [WITHDRAWN] (IASLC-WCLC 2025) - No abstract available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

Toxicity profiles of ROS1 tyrosine kinase inhibitors in advanced non-small cell lung cancer: a systematic review and proportional meta-analysis. (PubMed, Front Pharmacol) - "Systemic SAEs exhibited greater variability across agents, ranging from 29% to 47%: crizotinib, 43% (95% CI, 36%-49%); ceritinib, 41% (95% CI, 37%-45%); lorlatinib, 39% (95% CI, 25%-55%); entrectinib, 32% (95% CI, 28%-36%); repotrectinib, 29% (95% CI, 24%-33%); iruplinalkib, 44% (95% CI, 38%-50%); and unecritinib, 47% (95% CI, 38%-56%)...Taletrectinib and unecritinib were notably associated with hepatotoxicity...These findings will guide drug selection and safety monitoring, emphasizing the necessity of considering patients' health status, potential risk factors, and the characteristics of ROS1-TKI-related adverse reactions. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024551353, identifier CRD42024551353."

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

First Clinical Evidence of Repotrectinib Efficacy in ROS1-Rearranged NSCLC With a D2033N Resistance Mutation: Case Report. (PubMed, Clin Lung Cancer) - No abstract available

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

Exposure-Response Analysis of Repotrectinib to Support the Dose Recommendation for Patients With ROS1-Positive NSCLC or NTRK-Positive Solid Tumors. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "This work highlighted the importance of selecting appropriate exposure measures in exposure-response analyses, particularly when dose or dose frequencies change throughout treatment. The integrated exposure-response analyses provided a robust framework to support the repotrectinib dosing strategy."

Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

CA127-1072: A Study to Assess the Effect of Voriconazole and Quinidine on the Pharmacokinetics of a Single Dose of Repotrectinib in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2025 ➔ Dec 2024 | Trial primary completion date: Jul 2025 ➔ Dec 2024 | Recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date

Taletrectinib (Ibtrozi) - another kinase inhibitor for non-small cell lung cancer (NSCLC). (PubMed, Med Lett Drugs Ther) - No abstract available

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

NCCN has published NEW NCCN Guidelines in the NCCN Guidelines Navigator. This interactive digital tool can be used to navigate the current version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Uterine Neoplasms, Version 3.2025. (NCCN)

NCCN guideline • Microsatellite Instability • Uterine Cancer

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

ROS1 fusion-positive non-small cell lung cancer-repotrectinib as a new treatment option. (PubMed, Transl Cancer Res) - No abstract available

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

Discovery of imidazo[1,2-b]pyridazine derivatives as potent TRK inhibitors for overcoming multiple resistant mutants. (PubMed, Bioorg Chem) - "Tropomyosin receptor kinases (TRKs), the superfamily of transmembrane receptor tyrosine kinases, have recently attracted extensive attention as promising cancer therapeutic targets since the approval of Larotrectinib, Entrectinib and Repotrectinib by FDA. In addition, compound 15m displayed good oral bioavailability (F = 55.26 %). Collectively, compound 15m is a promising lead compound as a TRK inhibitor and deserves further structural optimization to address clinical refractory acquired resistances."

Journal • Oncology

PHARMACEUTICAL BENEFITS ADVISORY COMMITTEE (PBAC) MEETING OUTCOMES MAY 2025 PBAC MEETING: Augtyro for NSCLC (Pharmaceutical Benefits Scheme (PBS)) - "...The PBAC recommended PBS listing at an equivalent cost per day based on the steady state dosing of entrectinib and repotrectinib, with the price of the repotrectinib dose reduction pack to be derived on a weighted dose approach to maintain an equivalent cost per day to the steady state pack..."

Reimbursement • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Onco360 Has Been Selected as a National Specialty Pharmacy for Augtyro (repotrectinib) (The Manila Times) - "Onco360...has added Augtyro (repotrectinib) manufactured by Bristol Myers Squibb to its comprehensive list of limited distribution therapies."

Commercial • Non Small Cell Lung Cancer • Solid Tumor

Augtyro: Newly added patent in Orange Book (Orange Book) - Expiry on Jul 20, 2036

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

Recent advances in tropomysosin receptor kinase (TRK) inhibitors: a 2023-2024 patent landscape review. (PubMed, Expert Opin Ther Pat) - "TRK inhibitors like larotrectinib and entrectinib marked a paradigm shift - prioritizing molecular alterations over the tumor's anatomical location...Combination therapies with TRK inhibitors are emerging as a key strategy to enhance efficacy and overcome resistance. The FDA's recent approval of repotrectinib underscores progress in the TRK inhibitor landscape, while highlighting the continued need for innovation."

Journal • Review • Oncology • NTRK

Creating Repotrectinib Resistance in a Ba/F3 SLC34A2-ROS1 NSCLC cell line (EACR 2025) - "We generated three Ba/F3 SLC34A2-ROS1 repotrectinib resistant cell lines. A short term repotrectinib withdrawal makes the resistant cells more sensitive to repotrectinib. Mechanisms underlying the observed resistance such as mutations in the tyrosine kinase domain or in genes affecting alternative signaling pathways are currently being examined."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1 • SLC34A2

Assessment of two new ROS1+ NSCLC patient-derived cell lines as in vitro models for TKI resistance studies (EACR 2025) - "The IC50 values of unmutated ROS1+ Ba/F3 cells for crizotinib, entrectinib, lorlatinib, repotrectinib and zidesamtinib were 31.4; 44.6; 14.3; 14.9 and 29.9 nM, respectively...Interestingly, these cells were resistant to lorlatinib, while the patient is – after being treated with lorlatinib+cis-platinum+pemetrexed, now currently successfully treated with lorlatinib mono-therapy... In this study we showed that PC1 cells generated from a crizotinib-resistant patient were resistant to all ROS1 inhibitors tested. The G2032R mutated PC2 cells generated from a crizotinib and lorlatinib resistant patient were sensitive to repotrectinib, but not to zidesamtinib. This PC2 cell line can be used to assess off-target resistance mechanism to zidesamtinib."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • ARID1A • CD74 • PIK3CA • PIK3CG • ROS1