A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms (INCA 33989-101)

Research summary

Part 1a will consist of dose escalation using a statistical hybrid design to identify the MTD and/or RDE(s) of INCA033989 monotherapy in participants with MF or revised IPSET-thrombosis high-risk ET (TGA). After initial characterization of safety, PK, and pharmacodynamic effects of INCA033989 as monotherapy in TGA, dose escalation will start in TGB-MF SubOpt R, which encompasses participants with MF exhibiting suboptimal response to ruxolitinib. Participants enrolled in TGB-MF SubOpt R must be on a stable dose of ruxolitinib for at least 8 weeks prior to Cycle 1 Day 1 (1 dose reduction due to toxicities allowed). This dose should remain stable through the first cycle (ie, up to Day 28). The starting dose of INCA033989 will be 1 level lower than the highest safe dose level in TGA-MF at the time of participant recruitment. At each dose level, the first participant will be observed for ≥ 24 hours after administration of study drug before subsequent participants begin treatment with INCA033989. No more than 2 participants per dose level will begin treatment with INCA033989 within a 24-hour period. Part 1b will consist of a dose expansion in the 3 treatment groups at the identified RDE(s) as follows: • TGA-MF: INCA033989 monotherapy at each RDETGA-MF • TGA-ET: INCA033989 monotherapy at each RDETGA-ET • TGB-MF SubOpt R: combination therapy of INCA033989 at each RDETGB-MF and ruxolitinib (dose per label) Once all data collected during Parts 1a and 1b have been evaluated, and after the overall positive benefit/risk ratio of the study treatments has been confirmed, Part 1c will start. It will consist of a dose expansion with JAK inhibitor TxN participants at the RDE(s) defined below: • TGA-MF TxN: INCA033989 monotherapy at each RDETGA-MF • TGB-MF TxN: combination therapy of INCA033989 at each RDETGB-MF and ruxolitinib (dose per label) Participants will be randomly assigned to 1 of the TxN treatment groups. TGA-MF TxN participants may crossover to TGB-MF TxN if suboptimal response is observed after 12 weeks of INCA033989 monotherapy and the RDETGB-MF is already established.

Principal Investigator

Dr Bethan Psaila

Contact us

Email: Latephasehaematology@ouh.nhs.uk

IRAS number

1008102