This is a Phase 1, open-label, dose-escalation study of CBX-663 in participants with R/R AML, MDS or CMML (Cohort A), advanced solid tumors (Cohort B), or recurrent or progressive GBM (Cohort C) (collectively called 'indication cohorts'). Participants aged ≥18 years are planned to be enrolled. CBX-663 will initially be investigated on a fixed dosing schedule. CBX-663 will be administered intravenously (IV) on Cycle 1 Day 1 (C1D1) and then once weekly (QW) in 21-day cycles. Participants will continue treatment with CBX-663 until unacceptable toxicity, progressive disease, withdrawal of consent, or lack of clinical benefit.
R/R AML, as defined by standardized criteria (e.g., European Leukemia Net criteria (Dohner, 2022) (Arber, 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. Participants must have bone marrow blasts ≥5%.
R/R MDS as per WHO 2022. Participants must have peripheral or bone marrow blasts <20%, and must have exhausted locally available treatments, including treatments for actionable mutations.
R/R dysplastic or proliferative CMML participants, participants must be resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
Known or suspected leptomeningeal disease are excluded, defined as radiographic evidence of leptomeningeal involvement on MRI of the brain and/or spine, or positive cerebrospinal fluid (CSF) cytology, at screening or prior to first dose.
Tumors involving the brainstem or spinal cord are excluded, including primary tumors arising from, or metastatic lesions involving, the brainstem (midbrain, pons, or medulla) or spinal cord.
Received prior bevacizumab or any other anti-VEGF or anti-VEGFR therapy.
Absolute lymphocyte count <800/uL.
Single group
CBX-663
DrugIntravenous (I.V.) CBX-663
Recommended Phase 2 Dose (RP2D)
To determine the RP2D.
To determine safety and tolerability of CBX-663; Dose Limiting Toxicities (DLTs), Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs).
Frequency and type of dose-limiting toxicities (DLT), Frequency, duration, and severity of treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs), and serious adverse events (SAEs), Frequency and severity of cytokine release syndrome (CRS) adverse events (AEs), Withdrawal from the study, drug discontinuations, drug interruptions, or dose reductions due to adverse events Incidence/shifts of clinical laboratory abnormalities
To assess the PK of CBX-663: AUC0-t
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of CBX-663 and relevant metabolites.
To assess the PK of CBX-663: Cmax
Maximum plasma concentration (Cmax) of CBX-663 and relevant metabolites.
To assess the immunogenicity of CBX-663.
Incidence and severity of anti-drug antibodies (ADAs)
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