Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)

This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and
pharmacokinetics of ADCT-301 in patients with Acute Myeloid Leukemia (AML) or Acute
Lymphoblastic Leukemia (ALL).

ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a
pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells,
covalently cross links deoxyribonucleic acid (DNA) preventing replication.

The study will be conducted in 2 parts: In Part 1 (dose escalation) patients will either be
on weekly administration or every 3-week administration. Patients on weekly administration
will receive an infusion of ADCT-301 on Days 1, 8, and 15 of each 3 week treatment cycle.
Patients on 3-week administration will receive an infusion of ADCT-301 on Day 1, every 3
weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.

In Part 2 (expansion), patients will be assigned to receive a recommended dose and/or
schedule of ADCT-301 as determined by a Dose Escalation Steering Committee.

For each patient, the study will include a screening period (up to 28 days), a treatment
period, and a follow-up period to assess disease progression and survival for up to 12 months
after the last dose of study drug. The total study duration will be dependent on overall
patient tolerability to the study drug and response to treatment. It is anticipated that the
entire study (Parts 1 and 2) will enroll a maximum of 80 patients and could last
approximately 3 years from first patient treated to last patient completed.

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.

- Creatinine ≤1.5mg/dL.

- Serum/plasma 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/plasma bilirubin ≤1.5 times the upper limit of normal (ULN).

- Women of childbearing potential must have a negative urine or serum beta-human
chorionic gonadotropin pregnancy test within 7 days prior to Day 1.

- Women of childbearing potential must agree to use a highly effective method of
contraception. Men with female partners who are of childbearing potential must agree
that they or their partners will use a highly effective method of contraception.

- White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.

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.

- Pregnant or breastfeeding women.

- Significant medical comorbidities, including uncontrolled hypertension (diastolic
blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than
New York Heart Association class II), severe uncontrolled ventricular arrhythmias,
electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe
chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months
prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.

- Use of any other experimental medication(s) within 14 days or 5 half-lives but in no
case < 14 days prior to the start of the study treatment on Cycle 1, Day 1.

- Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and
any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted
therapies within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day
1 treatment, except if approved by the Sponsor.

- Failure to recover (to CTCAE Version 4.0 Grade 0 or Grade 1) from acute non
hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy),
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.