This study evaluates ADCT-301 in patients with relapsed/refractory Non-Hodgkin or Hodgkin
lymphoma. Patients will participate in a dose-escalation phase (Part 1) and receive
escalating doses of ADCT-301 every 3 weeks.
In Part 2 of the study, patients will receive a recommended dose(s) of ADCT-301 every 3
This is a Phase I, first in human clinical study with ADCT-301 to evaluate the safety and
tolerability and pharmacokinetics of ADCT-301 in patients with relapsed/refractory lymphoma.
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) up to 80 patients 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) up to 60 patients will be assigned to receive the recommended dose(s)
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) could last approximately 3 years from first patient treated to
last patient completed.
1. Male or female age 18 years or older.
2. Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification
3. Pathologically confirmed relapsed or refractory lymphoma
4. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
5. Measurable disease, defined by the 2014 Lugano Classification Criteria
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. Absolute neutrophil count ≥1500/µL.
8. Platelet count of ≥75000/µL.
9. Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
10. Creatinine ≤1.5mg/dL
11. Serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase
≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone
12. Total serum bilirubin ≤1.5 times ULN
13. Women of childbearing potential must have a negative serum beta-human chorionic
gonadotropin pregnancy test within 7 days prior to Day 1.
14. 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.
1. Patients who have an option for any treatment with proven clinical benefit for their
lymphoid malignancy at current state of disease.
2. Active graft-versus-host disease.
3. Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1.
4. Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow
cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
5. Known history of positive serum human anti-drug antibody (ADA), or known allergy to
any component of ADCT-301
6. History of symptomatic autoimmune disease
7. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen
(HbsAg), or antibody to hepatitis C virus (anti-HCV)
8. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
9. Pregnant or breastfeeding women.
10. Significant medical comorbidities, including uncontrolled hypertension (diastolic
blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure
(greater than New York Heart Association class II), severe uncontrolled ventricular
arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled
diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial
infarction within 6 months prior to screening, or uncontrolled atrial or ventricular
11. Use of any other experimental medication(s) within 14 days prior to start of the study
12. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy (including
prednisone ≥ 40 mg/day or equivalent) within 14 days or 5 half-lives (whichever is
shorter) prior to Cycle 1, Day 1 treatment.
13. Failure to recover (to Common Terminology Criteria for Adverse Events [CTCAE Version
4.0] Grade 0 or Grade 1) from acute non-hematologic toxicity (except alopecia or Grade
2 or lower neuropathy), due to previous therapy, prior to Screening.
14. Congenital long QT syndrome or a corrected QTc interval ≥ 470 ms at screening
15. 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
16. Any other significant medical illness, abnormality, or condition