Approval of larotrectinib (Vitrakvi) was based on overall response rate and response duration in the first 55 patients with unresectable or metastatic solid tumors harboring an NTRK gene fusion enrolled across three multicenter, open-label, single-arm clinical trials. The ORR was 75% (95% confidence interval, 61%-85%), including 22% complete responses and 53% partial responses. At the time of database lock, median duration of response had not been reached, the FDA said.
The most common tumors were salivary gland tumors (22%), soft tissue sarcomas (20%), infantile fibrosarcomas (13%), and thyroid cancers (9%). Identification of positive NTRK gene fusion status was prospectively determined in local laboratories using next-generation sequencing or fluorescence in situ hybridization.
Results of the three trials, a phase 1 trial among 8 adult patients (), a phase 1/2 trial among 12 pediatric patients ( ), and a phase 2 basket trial among 35 adult and adolescent patients ( ), were at the annual meeting of the American Society of Clinical Oncology in 2017.
The safety of larotrectinib was evaluated in 176 patients enrolled across the three clinical trials, including 44 pediatric patients. The most common adverse reactions with larotrectinib were fatigue, nausea, dizziness, vomiting, increased AST, cough, increased ALT, constipation, and diarrhea, the FDA said.
The recommended larotrectinib doses are 100 mg orally twice daily for adults and 100 mg/m2 orally twice daily (maximum of 100 mg per dose) for pediatric patients.
The approval of larotrectinib follows the approval of pembrolizumab for certain solid tumors with the MSI-H biomarker, as the first approval for the treatment of cancer based on a biomarker rather than the particular body part or organ system affected by the tumor.