8 Olverembatinib
A third-generation TKI
Every other day dosing (QOD)
AEs: Skin pigmentation, hypertriglyceridemia
8.1 Phase 1b (Jabbour et al. 2025)
8.2 POLARIS-2
CML-CP
Part A: CML-CP pts (previously treated with >2 TKIs) N-285. Randomized 2:1 with bosutinib. Drug dose is 30 mg QOD
Part B: CML-CP with T315I (previosly treated with > 2KIs). Drug dose is 40 mg QOD
8.3 Clinical data — Li 2026 (ChiCTR2200061655)
Per [[sources/li-2026-olverembatinib-2L-cp-cml-asco-abstract|Li 2026 ASCO #6510]] (single-arm, multicenter China; n=47; data 4 Aug 2022 – 14 Jan 2026):
8.3.1 Population
- CP-CML resistant (91.5%) / intolerant (8.5%) to first-line TKIs, without T315I.
- Median age 42; first-line imatinib 25.5%, 2G-TKI 74.5%; baseline non-T315I mutations 23.4%.
8.3.2 Efficacy (42 evaluable)
- CCyR 76.2%; MMR 47.6%; MCyR 83.3%; CHR 83.3%.
- Progressive deepening to cycle 24: CCyR 91.3%, MMR 60.9%.
- 2G-TKI-pretreated subset (n=32): CCyR 81.3%, MMR 50%.
- Median treatment duration 16 cycles.
8.3.3 Safety
Any-grade TRAEs 89.4%; grade ≥3 TRAEs 44.7%; SAEs 12.8%.
Skin hyperpigmentation 51.1% (signature), hyperuricemia 31.9%, CPK increased 27.7% (mostly grade 1-2).
Grade ≥3 hematologic: thrombocytopenia 42.6%, neutropenia 25.5%, anemia 8.5%.
8.4 Only 2 grade-1 hypertension CV events; no deaths.
8.5 POLARIS-1
Olverembatinib + Venetoclax or Reduced intensity chemotherapy in newly diagnosed ph positive ALL
Olverembatinib plus blinatumomab (chemo-free)
N=300