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Clinical Data

BAY 2731954 (LOXO-195) has been used to treat two patients (1 adult patient with colorectal cancer and 1 paediatric patient with infantile fibrosarcoma) whose tumours developed solvent-front substitution-mediated acquired resistance to larotrectinib (G595R and G623R mutation, respectively)[1]. Both patients had rapid tumour responses to BAY 2731954 (LOXO-195), and overall duration of disease control was extended.

These cases demonstrate that BAY 2731954 (LOXO-195) could abrogate resistance in cancers with NTRK gene fusion that acquire kinase domain mutations, suggesting a potential approach for sequential treatment with TRK inhibitors [1].

References

  1. Drilon A, Nagasubramanian R, Blake JF et al. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov 2017; 7: 963-972.

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