Clinical Trial 23675

• Overview

  Study Title:

  A Phase 1, Open-Label, Dose-escalation Study to Evaluate Safety, Tolerability, and Clinical Activity of CBX-250 in Participants with Relapsed or Refractory Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia.

  Objective:

  Primary Objective: Secondary Objectives:

• Treatments

  Therapies:

  Bispecific antibody of the IgG1 isotype

  Medications:

  CBX-250 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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.
  • Participants with histological confirmation of advanced hematologic malignancy.
  • White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
  • Historical documented evidence of HLA-A*02:01 allele positivity.
  • ECOG PS score 0-1 (if aged ≥18 years); Karnofsky Performance Scale of ≥70 (if aged ≥16 years and > Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia.
  • 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).
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.
  • Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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.
  • Active hepatitis B infection (participants with documented clearance following treatment are allowed).
  • Active hepatitis C infection (participants with documented clearance following treatment are allowed).
  • Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Cardiac Disease: Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class >II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. QTc using Fridericia's correction (QTcF) >480 msec
  • Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
  • Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
  • History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate.
  • Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
  • Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
  • Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
  • Known allergy or sensitivity to study drug, including excipients.

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.