A phase 2 study of tipifarnib in children and young adults with tumors harboring HRAS genomic alterations: NCI-COG Pediatric MATCH trial (APEC1621M).
Christine A Pratilas, Marielle E Yohe, Paul M Williams et al.
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In 30 seconds
This phase 2 NCI-COG Pediatric MATCH study evaluated intermittent oral tipifarnib in children and young adults with relapsed or refractory solid tumors carrying specified HRAS mutations. Five of seven patients matched to the treatment arm enrolled: four had rhabdomyosarcoma and one angiosarcoma. No objective responses occurred; one patient had stable disease after cycle 2 and received four cycles. Adverse events were generally consistent with prior experience, and severe events reported on treatment were attributed to disease progression rather than protocol therapy. Enrollment was lower than anticipated, and the study closed before accrual was complete.
Key findings
- Five of seven patients matched to the tipifarnib arm enrolled; diagnoses were rhabdomyosarcoma (n = 4) and angiosarcoma (n = 1).
- There were no objective responses; one patient had stable disease at the end of cycle 2 and remained on treatment for 4 cycles.
- Grade 1/2 adverse events were consistent with those expected from prior studies; grade 3 or higher events reported on treatment were not related to protocol therapy.
Why it matters
The study demonstrates that molecular screening can identify children with HRAS-altered tumors for biomarker-selected trials, while also showing the difficulty of enrolling this population. The absence of objective responses and limited disease control provide useful evidence about single-agent tipifarnib in these refractory pediatric tumors and help frame the need for further therapeutic investigation.
What to keep in mind
Only five patients enrolled, and the study closed before accrual was complete, limiting assessment of efficacy in this biomarker-selected population.