Study CBX-250-001 is a Phase 1, open-label, dose-escalation study of CBX-250 in participants with relapsed/refractory AML, HR-MDS, CMML, and CML. Participants aged ≥ 12 years are planned to be enrolled. CBX-250 will initially be investigated on a fixed step-up dosing schedule. CBX-250 will be administered subcutaneously in 28-day cycles, with the first study drug dose administered on Cycle 1, Day 1. Cycle 1 will consist of a priming phase over 7 days, and a target phase over 28 days. Participants will continue CBX-250 until progressive disease (PD) or unacceptable toxicity. All subsequent treatment cycles will be 28 days.
Dose Escalation: Male or female participants aged ≥18 years.
Backfill Cohorts: Male or female participants aged ≥12 years for whom no curative treatment options, including transplantation, are available.
R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria [Dohner 2022]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible.
R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
Isolated extramedullary relapse.
Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy).
Known HIV infection.
Sequential
CBX-250
Drugsubcutaneous CBX-250
To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.
Frequency and type of DLT
To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.
Frequency, duration, and severity of TEAEs, TRAEs, AESIs, and SAEs
To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.
Frequency and severity of CRS AEs
To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.
Drug withdrawals, drug interruptions, or dose reductions due to adverse events
AUC0-t (first dose and at steady state)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of CBX-250 and relevant metabolites
Cmax
Maximum plasma concentration (Cmax) of CBX-250 and relevant metabolites
Tmax
Time to observed maximum plasma concentration of CBX-250 and relevant metabolites
ADAs
Incidence and severity of anti-drug antibodies
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