A Study of CBX-250 in Participants With Relapsed or Refractory Myeloid Leukemias

Inclusion Criteria

• •Participants are eligible to be included in the study only if all of the following criteria apply:
• •Age
• •1. Dose Escalation: Male or female participants aged ≥18 years.
• •2. Backfill Cohorts: Male or female participants aged ≥12 years for whom no curative treatment options, including transplantation, are available.
• •Diagnosis \& Disease Characteristics
• •3. Participants with histological confirmation of advanced hematologic malignancy including:
• •1. 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.
• •2. 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).
• •3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
• •4. White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
• •5. Historical documented evidence of HLA-A\*02:01 allele positivity.
• •Performance Level
• •6. ECOG PS score 0-1 (if aged ≥18 years); Karnofsky Performance Scale of ≥70 (if aged ≥16 years and \<18 years); Lansky PS of ≥70 (if aged \<16 years).
• •Prior Therapy
• •7. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia.
• •8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
• •9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
• •10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
• •11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions:
• •* Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval.
• •* Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
• •12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
• •13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or ≤Grade 1.
• •14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician.
• •Adequate Organ Function Requirements within 10 Days of Treatment Initiation
• •15. Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults).
• •1. Participants ≥18 years: glomerular filtration rate ≥45 mL/min
• •2. Participants \<18 years: ≥45 mL/min x (participant's body surface area m2/1.73) • Adequate liver function defined as:
• •* Total bilirubin \<1.5 × the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions.
• •* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 × ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician).
• •Sex and Contraceptive/Barrier Requirements
• •16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
• •17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.
• •Informed Consent
• •18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.