Abemaciclib (CDK4/6) + temozolomide/irinotecan delivers durable CR in 5th-relapse ARMS

Abemaciclib is an oral CDK4/6 inhibitor; in JPCS Part A (Phase 1b, NCT04238819) an 8-year-old with 5th-relapse, PAX3-FOXO1, CDK4-amplified ARMS received abemaciclib 55 mg/m² BID continuously with temozolomide 100 mg/m² and irinotecan 50 mg/m² on days 1–5 of 21-day cycles; CR occurred by day 78, with 22.6-mo DOR and 23.7-mo PFS after 12 cycles of triplet then 23 cycles of abemaciclib alone; AEs were mainly grade 1 GI and grade 3 neutropenia, no DLTs. In contemporary salvage, VIT (vincristine/irinotecan/temozolomide) achieves ORR 44% (vs VI 31%) and improves OS (HR 0.55) but with ≥G3 AEs in 98%—and CDK4 amplification, present in ~25% of PAX3-FOXO1 ARMS, provides a biologic rationale for CDK4/6 targeting in this subset.