Clinical Trial 24247

• Overview

  Study Title:

  A Phase 1, Open-Label, Dose-Escalation Study to Evaluate Safety, Tolerability, and Clinical Activity of CBX-663 in Participants with Relapsed or Refractory Myeloid Malignancies, Advanced Solid Tumors, or Recurrent or Progressive Glioblastoma

  Summary:

  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.

  Objective:

  Primary Objective: To determine the Recommended Phase 2 Dose (RP2D) of CBX-663 based on safety and tolerability, preliminary efficacy, PK and PD in participants with R/R AML, MDS or CMML (Cohort A), participants with advanced solid tumors (Cohort B), and participants with recurrent/progressive GBM (Cohort C). To determine safety and tolerability of CBX-663. To assess the PK of CBX-663. To assess the preliminary anti-leukemic activity of CBX-663 in participants with R/R AML, MDS or CMML (Cohort A). To assess the preliminary anti-tumor activity of CBX-663 in participants with advanced solid tumors based (Cohort B) on Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. To assess the preliminary anti-tumor activity of CBX-663 in participants with recurrent/progressive GBM (Cohort C). Secondary Objectives: To assess the immunogenicity of CBX-663.

• Treatments

  Therapies:

  IgG1-based bispecific antibody targeting TERT peptide-HLA complex and CD3

  Medications:

  CBX-663 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Aged ≥18 years.
  • Backfill Cohorts: Participants for whom no curative treatment options, including transplantation, are available.
  • Historical documented evidence of HLA-A*02:01 allele positivity.
  • ECOG PS score 0-1. Adequate Organ Function Requirements within 10 Days of Treatment Initiation.
  • Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 based on local institutional practice (e.g., Cockcroft-Gault formula).
  • Adequate liver function.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Previous treatment with any pHLA-targeting 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).
  • Any acute or chronic infection requiring systemic treatment.
  • 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.
  • Graft-Versus-Host Disease (GVHD): Active GVHD.
  • 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 (e.g., 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.
  • Current or historical diagnosis of a gastrointestinal autoimmune or inflammatory condition, including but not limited to ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis, or microscopic colitis (collagenous or lymphocytic colitis), or a history of GI toxicity from previous therapy that, in the opinion of the investigator, should preclude study participation.
  • Significant impairment of lung function requiring chronic use of ambulatory supplemental oxygen.
  • Screening laboratory values or investigations that do not meet the requirements for adequate organ function.
  • 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 or anti-cancer therapy other than CBX 663, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
  • Participants who experienced severe, life-threatening or recurrent (≥ Grade 2) immune-mediated adverse events or infusion-related reactions including those that led to permanent discontinuation while on previous treatment with immuno-oncology agents.
  • Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted. Participants who stopped calcineurin inhibitor (CNI) prophylaxis should be off CNI for at least 4 weeks.
  • Known allergy or sensitivity to study drug, including excipients.

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