^
    21d
    Repotrectinib Post-Marketing Surveillance in Korean Patients With ROS1-Positive Non-Small Cell Lung Cancer (NSCLC) or Solid Tumors Harboring a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion (clinicaltrials.gov)
    P=N/A, N=10, Not yet recruiting, Bristol-Myers Squibb
    New trial
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ROS1 fusion • ROS1 positive
    |
    Augtyro (repotrectinib)
    22d
    Phase Ib of repotrectinib plus osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer. (PubMed, Lung Cancer)
    Osimertinib plus repotrectinib showed safety and promising icORR. Results were comparable to new combinations, considering heavily pretreated patients. Efficacy in biomarker-selected NSCLC patients requires further investigation.
    P1 data • Journal
    |
    EGFR (Epidermal growth factor receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • YAP1 (Yes associated protein 1)
    |
    EGFR mutation
    |
    Tagrisso (osimertinib) • Augtyro (repotrectinib)
    1m
    Characterization and clinical management of adverse events following treatment with repotrectinib: a TRIDENT-1 analysis. (PubMed, Oncologist)
    Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.
    Journal • Adverse events
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ROS1 fusion • ROS1 positive • NTRK positive • NTRK fusion
    |
    Augtyro (repotrectinib)
    1m
    A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients (clinicaltrials.gov)
    P2, N=60, Recruiting, Teligene US | Trial completion date: Apr 2027 --> Dec 2028 | Trial primary completion date: Aug 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    TL118
    2ms
    Characterization and Clinical Management of Adverse Events Following Treatment with Repotrectinib: A TRIDENT-1 Analysis. (PubMed, Oncologist)
    Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.
    Journal • Adverse events
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ROS1 fusion • ROS1 positive • NTRK positive • NTRK fusion
    |
    Augtyro (repotrectinib)
    3ms
    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=30, Completed, Bristol-Myers Squibb | Recruiting --> Completed
    Trial completion
    |
    Augtyro (repotrectinib) • metformin • omeprazole
    3ms
    Next generation sequencing guided treatment of ALK tyrosine kinase inhibitor induced long survival in lung squamous cell carcinoma harboring ROS1 gene fusions: a case report and literature review. (PubMed, Front Med (Lausanne))
    Peripheral monocyte profiling of the patient post-Repotrectinib and localized radiotherapy showed 75% CD8+/CD3 + T cells, 14.2% CD4+/CD3 + T cells, 3.95% regulatory T cells (Tregs), and 38% PD-1 + CD3 + T cells...Furthermore, we also provide a comprehensive review of recent clinical advancements in ALK/ROS1-TKI for NSCLC, including mechanistic insights into TKI resistance development. This case underscores the therapeutic potential of molecular-targeted agents in LUSC and highlights the essential role of NGS-guided precision oncology.
    Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • EGFR mutation • ALK mutation • ROS1 fusion • ROS1 rearrangement
    |
    Augtyro (repotrectinib)
    4ms
    Discovery of new non-macrocyclic TRK inhibitors based on conformational flexibility and scaffold hopping to overcome clinical acquired resistance. (PubMed, Bioorg Chem)
    The best TRK inhibitor 5c had IC50 values of 0.75 and 0.96 nM against TRKAG595R and TRKAG667C, showing better potency than drugs larotrectinib (approximately 87- and 46-fold improvement) and selitrectinib (approximately 10- and 13-fold improvement). More importantly, 5c demonstrated favorable in vivo pharmacokinetic properties and antitumor efficacy (tumor growth inhibition (TGI) of 91% at 30 mg/kg and 115% at 60 mg/kg with 4 of 6 partial regression) in a BaF3-TMP3-TRKAG667C xenograft mouse model, which is greatly superior to that of selitrectinib (TGI of 2% at 30 mg/kg). Compound 5c exhibits significant potential to overcome clinical acquired multiple resistance to TRK inhibitors.
    Preclinical • Journal
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    NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK fusion
    |
    Vitrakvi (larotrectinib) • selitrectinib (BAY 2731954)
    4ms
    Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial. (PubMed, Nat Med)
    These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .
    P1/2 data • Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK positive • NTRK fusion
    |
    Augtyro (repotrectinib)
    5ms
    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, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Augtyro (repotrectinib) • metformin • omeprazole