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). 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 .
- 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.