Clinical Trial 23479

• Overview

  Study Title:

  A Multicenter, Open-Label Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of BL-M11D1 in Patients with Relapsed/Refractory Acute Myeloid Leukemia

  Objective:

  Primary Objectives: To assess the safety and tolerability of BL-M11D1 in AML. To determine the minimum safe and effective dose (MSED), maximum tolerated dose (MTD) if reached, and maximum administered dose (MAD)of BL-M11D1 in AML. Secondary Objectives: To characterize the pharmacokinetics (PK) of BL-M11D1, total anti-CD33 antibody, and payload (Ed-04). To investigate the anticancer activity of BL-M11D1. To evaluate the preliminary efficacy of BL-M11D1 in subjects with relapsed/refractory acute myeloid leukemia.

• Treatments

  Therapies:

  Antibody-Drug Conjugate

  Medications:

  BL-M11D1 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Signed the informed consent voluntarily and agreed to follow the program requirements.
  • Age ≥18 years.
  • Has a life expectancy of ≥3 months.
  • Relapsed and/or refractory CD33-positive AML as determined by pathology review at the treating institution that has failed initial standard of care therapy.
  • Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2.
  • Toxicity of previous anticancer therapy has returned to Grade ≤1 as defined by NCI-CTCAE V5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2.
  • Has adequate liver and renal function before registration.
  • Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix D) during the course of the study and for 7 months after the last dose of study treatment. An additional contraceptive method, such as a barrier method (eg, condom), is recommended.
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female subjects are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman >45 years old in the absence of other biological or physiological causes. In addition, females 40 mIU/mL to confirm menopause.
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Subjects with acute promyelocytic leukemia (APL) or chronic myelogenous leukemia in blast crisis (CML).
  • Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anticancer therapy within 2 weeks or 5 half-lives (3 half-lives for antibodies) (whichever is longer) prior to the first administration, mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration, or palliative radiotherapy within 2 weeks prior to the first administration.
  • Subjects with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure, history of transmural myocardial infarction, unstable cardiac arrhythmias or angina pectoris, etc.
  • Subjects with prolonged QT interval (QTcF >470 msec), complete left bundle branch block, Grade 3 atrioventricular block.
  • Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for Type I diabetes, hypothyroidism that can be controlled only by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
  • Subjects with other prior or concurrent malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection, or other malignancy in which treatment does not interfere with the safety or efficacy assessment of the investigational product.
  • Subjects with resistant and refractory hypertension or uncontrolled hypertension despite ≥3 different types of antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg).
  • Subjects with active acute or chronic graft vs. host disease (aGVHD or cGVHD) should be excluded from this study. Subjects with GVHD who are receiving treatment with systemic glucocorticoids >10 mg/day equivalent of prednisone should also be excluded from the study; however, treatment with low-dose glucocorticoids (≤10 mg/day equivalent of prednisone) is permitted.
  • Subjects currently receiving immunosuppressive therapy should be excluded from this study.
  • Clinical evidence of disseminated intravascular coagulation (DIC). Smoldering low-grade DIC is allowed after discussion with the sponsor.
  • Subjects with stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event or thromboembolic event (eg, deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 6 months before randomization except for those with a diagnosis of DVT who are stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before randomization. Infusion set-related thrombosis is excluded.
  • Subjects with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgment. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
  • Subjects with pre-existing ≥Grade 2 peripheral neuropathy.
  • Subjects with Grade ≥3 lung disease defined by CTCAE v5.0.
  • Other criteria may apply.

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