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

Exceptional response to sequential TRK inhibition in an epithelioid glioblastoma with NOS1AP-NTRK1 fusion (EANO 2026) - "First-line therapy consisted of standard radiochemotherapy with concomitant and adjuvant temozolomide from April to October 2021...Lomustine + bevacizumab was ineffective (PFS: 2 months)... Sequential NTRK-targeted therapy can produce exceptional and durable responses in NTRK1 fusion-positive eGB. Larotrectinib was initiated after progression based on the presence of a NOS1AP-NTRK1 fusion, targeting constitutive TRKA activation and downstream MAPK and PI3K-AKT signaling, resulting in rapid antitumor effects. Upon progression, repotrectinib, a CNS-penetrant second-generation TRK inhibitor, was selected to overcome potential resistance mutations and maintain pathway inhibition."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BRAF • NTRK • NTRK1

Addition of Chemotherapy to Targeted Therapy at Progression in RET- and ROS1-Rearranged NSCLC: Insights From a Case Series and Therapeutic Implications (IASLC-WCLC 2026) - "He experienced rapid disease progression after 4 weeks of first-line selpercatinib...In the absence of actionable resistance alterations, platinum-based chemotherapy was introduced, leading to a complete response.The third patient, a 60-year-old never-smoker, presented with advanced ROS1-rearranged lung adenocarcinoma (PD-L1 5%) and had been heavily pretreated with multiple tyrosine kinase inhibitors, including entrectinib, repotrectinib, and lorlatinib...In this context, the addition of chemotherapy to ongoing targeted therapy at progression appears to be a feasible and effective strategy to overcome resistance across RET- and ROS1-rearranged NSCLC. Nevertheless, prospective studies are needed to better define the role of this approach and to identify patients at increased risk of primary resistance, including those with smoking exposure or tumours harbouring co-mutations."

Clinical • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • KIF5B • PD-L1 • PTEN • RET • ROS1 • TP53

Tumor-Agnostic and Histology-Tuned Targeted Therapies in Gastrointestinal Cancers: NTRK and RET Fusions and the Evolving Role of Molecular Basket Strategies. (PubMed, J Gastrointest Cancer) - "In the initial 55-patient larotrectinib analysis, ORR was 75% by independent review and 80% by investigator assessment; the subsequent expanded pooled analysis reported an investigator-assessed ORR of 79%...Mature TRIDENT-1 data support repotrectinib in both TRK inhibitor-naive and pretreated disease, including solvent-front mutations. Selpercatinib received traditional US approval in July 2026, whereas zenocutuzumab provides GI-specific options for NRG1 fusion-positive pancreatic and biliary cancers...Practical implementation requires quantitative prevalence estimates, appropriately selected DNA- and RNA-based testing, recognition of false-positive and false-negative pan-TRK immunohistochemistry, molecular tumor-board interpretation, timely access, and resistance-informed reprofiling. Tumor-agnostic approvals create opportunities, but GI-specific biology determines how reliably and when those opportunities should be used."

Journal • Review • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • MSI • NRG1 • NTRK • RET

Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - P1/2 | "Repotrectinib had durable clinical activity in patients with ROS1 fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.)."

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

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

Adverse events • Oncology

Investigation of the effect of formulated sodium lauryl sulfate on microenvironment-driven dissolution of repotrectinib immediate-release capsules. (PubMed, J Pharm Sci) - "This mechanism provides a scientific basis for understanding dissolution behavior in highly surfactant-loaded formulations and explains the reduced sensitivity of conventional dissolution testing to moderate formulation changes. The findings provide important considerations for dissolution method development, interpretation of discriminating capability, and regulatory assessment of surfactant-containing oral drug products."

Journal • CNS Disorders • Psychiatry

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 I/II ARROS-1 study of zidesamtinib (NVL-520) in ROS1 fusion-positive solid tumours (ESMO 2024) - P1/2 | "Pts had a median of 3 (range: 1-11) prior anticancer therapies, including any ROS1 TKI (99%); lorlatinib (55%), repotrectinib (repo; 21%), or either (67%); ≥2 ROS1 TKIs (69%); and chemo (66%). Zidesamtinib demonstrated encouraging efficacy and durability in pts with pretreated ROS1+ NSCLC, including those who had exhausted available therapies, with ROS1 resistance mutations including G2032R, and/or with CNS mets. Safety was favorable and consistent with the highly ROS1-selective and TRK-sparing design. Ph 2 enrollment is ongoing with registrational intent in pts with TKI-naïve and pretreated ROS1+ NSCLC."

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

Repotrectinib in tyrosine kinase inhibitor (TKI)-naïve patients (pts) with advanced ROS1 fusion-positive (ROS1+) NSCLC in the phase 1/2 TRIDENT-1 trial: Clinical update, treatment beyond progression and subsequent therapies. (ASCO 2024) - P1/2 | "With a median follow-up of ~3 years in TRIDENT-1, repotrectinib continued to demonstrate durable clinical activity in ROS1 TKI-naïve pts. Progression patterns and treatment beyond progression were described for the first time."

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

Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 ."

Journal • P1/2 data • Oncology • Solid Tumor • NTRK • 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

Pivotal Data Update from the Phase 1/2 TRIDENT-1 Trial of Repotrectinib in Patients with ROS1+ Advanced Non-Small Cell Lung Cancer (NSCLC) (IASLC-TTLC 2023) - P1/2 | "With a longer follow-up, repotrectinib remains well tolerated with a manageable safety profile. Efficacy and safety were generally consistent across age subgroups."

Clinical • Metastases • P1/2 data • Anemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • ROS1

Repotrectinib in Patients with ROS1 Fusion-positive (ROS1+) NSCLC: Update from the Pivotal Phase 1/2 TRIDENT-1 Trial (IASLC-WCLC 2023) - P1/2 | "With 14 months' minimum follow-up in TRIDENT-1, repotrectinib continued to demonstrate durable efficacy in patients with ROS1+ NSCLC, including intracranial activity, in both TKI-naïve and 1 prior TKI and no chemo cohorts. Safety in patients treated at RP2D was manageable, consistent with previous reports in all treated patients."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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

FDA Approval Summary: Repotrectinib for locally advanced or metastatic ROS1-positive non-small cell lung cancer. (PubMed, Clin Cancer Res) - P1/2 | "The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs."

FDA event • Journal • Metastases • Ataxia • CNS Disorders • Cognitive Disorders • Constipation • Developmental Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor • ROS1

Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC) (AACR-NCI-EORTC 2022) - P1/2 | "He played a monumental role in developing repotrectinib, lazertinib, amivantamab, and other targeted- and immuno-therapies, many of which were acknowledged for breakthrough therapy designation and FDA approval. Repotrectinib achieves durable activity, including intracranial responses, in TKI-naïve and TKI-pretreated patients with ROS1+ advanced NSCLC, and those with ROS1 G2032R. Repotrectinib safety is well characterized, manageable, and compatible with long-term use."

Clinical • Late-breaking abstract • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

The FAK/SRC axis mediates resistance to KRAS G12C inhibitors and its blockade can overcome KRAS inhibitor resistance (AACR 2024) - "KRAS G12C inhibitors, sotorasib and adagrasib are FDA approved for locally advanced or metastatic KRAS G12C-positive NSCLC...Using a xenograft model of human KRAS mutant NSCLC, we determined that the combination of repotrectinib, a FAK/SRC inhibitor, and a KRAS G12C inhibitor significantly suppressed tumor growth as compared to KRAS G12C inhibitors alone, and this combination was well tolerated. Overall, our findings indicate that activation of FAK is a key mechanism of adaptive feedback and acquired resistance to KRAS G12C inhibitors in KRAS G12C-positive NSCLC and highlight the therapeutic potential of FAK/SRC inhibitors in combination with KRAS G12C inhibitors. These data support the clinical testing of the combination of FAK/SRC inhibitors and KRAS G12C inhibitors in patients with KRAS G12C-positive NSCLC."

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

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

Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1. (ASCO 2023) - P1/2 | "In TRIDENT-1, repotrectinib showed durable clinical activity in ROS1 TKI-naïve and -pretreated pts with or without BL CNS mets, including intracranial responses. Repotrectinib safety profile was similar in pts with ROS1+ NSCLC with or without CNS mets. Clinical trial information: NCT03093116."

Clinical • Metastases • P1/2 data • Alzheimer's Disease • Ataxia • CNS Disorders • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Pain • 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

Safety and preliminary clinical activity of NVL-520, a highly selective ROS1 inhibitor, in patients with advanced ROS1 fusion-positive solid tumors (AACR-NCI-EORTC 2022) - P1/2 | "Rationally designed ROS1 tyrosine kinase inhibitors (TKIs) that surpass the limitations of FDA/EMA-approved (crizotinib/entrectinib) or other investigational agents are a medical need. The novel ROS1 TKI NVL-520 is highly selective and designed to avoid the neurologic toxicities associated with ROS1 TKIs that concurrently inhibit TRK (entrectinib/repotrectinib/taletrectinib)...Patients received a median of 3 (range: 1-9) prior anticancer therapies, including any ROS1 TKI (100%); investigational ROS1 TKI (85%, including lorlatinib in 55%, repotrectinib in 40%); ≥2 ROS1 TKIs (75%); any chemotherapy (80%); ≥2 lines of chemotherapy (50%)... NVL-520 has been well-tolerated up to 100 mg daily with favorable pharmacokinetics. Activity has been demonstrated in heavily pretreated patients (of whom 70% received ≥2 prior ROS1 TKIs plus chemotherapy), including those with brain metastases and the G2032R mutation."

Clinical • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • 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 2026 ➔ Feb 2027

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

The information-seeking behaviour of health care providers for drug-drug interaction signals with lung cancer agents (ELCC 2025) - "The five most queried lung cancer drugs were repotrectinib (25%), osimertinib (17%), paclitaxel (14%), lorlatinib (11%) and afatinib (6%). The results show that HCPs find a clinically relevant interaction in almost half of all queries. The data give insights of the global population's commonly used lung cancer drugs and comedications. The information could serve both educational activities on DDIs and prioritize DDI studies with lung cancer agents."

Lung Cancer • Oncology • Solid Tumor

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

Osimertinib plus repotrectinib phase I trial in TKI-resistant non-small cell lung cancer (NSCLC) with EGFR mutations. (ASCO 2025) - P1 | "The findings prompted us to carry out the current study with osimertinib plus TPX-0005, which inhibit Src/FAK/JAK2, in addition to ALK, ROS1 and NTRKs. In Part Ia osimertinib + repotrectinib showed impressive intracranial ORR with a manageable safety profile. Part Ib with repotrectinib 160 mg BID plus osimertinib 80 mg is ongoing. Updated results will be presented."

P1 data • Anemia • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CDK4 • EGFR • FAT1 • FGFR3 • MET • MYC • PIK3CA • ROS1 • STAT3 • TP53 • YAP1