SHS_492311 PAGJ CADC 15261
A Phase 1, Open-label, Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Activity of ADCT-301 in Patients With Relapsed or Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia
This study evaluates ADCT-301 in patients with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). Patients will participate in a dose-escalation phase (Part 1) and receive ADCT-301 every 3 weeks. In Part 2 of the study, patients will receive a recommended dose of ADCT-301 every 3 weeks.
Select Inclusion Criteria:
Relapsed or refractory CD25-positive AML [per World Health Organization (WHO)].
Relapsed or refractory CD25-positive ALL [per World Health Organization (WHO)].
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement.
Total serum bilirubin ≤1.5 times the upper limit of normal (ULN).
Women of childbearing potential must not be pregnant must agree that they or their partners will use a highly effective method of contraception.
Select Exclusion Criteria:
Patients who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease.
Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.
Active graft-versus-host disease.
Autologous or allogenic transplant within the 60 days prior to Screening.
Known history of immunogenicity or hypersensitivity to a CD25 antibody.
Known history of positive serum human ADA, or known allergy to any component of ADCT-301.
Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy.
History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
Significant medical comorbidities (see protocol for specifics).
Use of any other experimental medication(s) within 14 days or 5 half-lives.
Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea and steroids), radiotherapy, or biotherapy targeted therapies within 21 days prior to the Day 1 visit, except if approved by the Sponsor.
Failure to recover (to Grade 0 or Grade 1) from acute non hematologic toxicity, due to previous therapy, prior to Screening.
Isolated extramedullary relapse (i.e., testicular, CNS).
Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening (unless secondary to pacemaker or bundle branch block).
Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy.
Any other significant medical illness, abnormality, or condition.
John Pagel, M.D.