This study evaluates the safety, tolerance, pharmacokinetics (PK), and antitumor activity of
ADCT-601 in patients with advanced solid tumors.
This is a Phase 1 open-label, multicenter single-arm study with a dose-escalation phase (Part
1) followed by a dose-expansion phase (Part 2). The study will enroll approximately 75
patients. A standard 3+3 dose-escalation design will be used for Part 1 in order to determine
the MTD and/or recommended dose for expansion (RDE).
Part 2 will consist of 3 cohorts from one or more selected tumor types. Each cohort will
enroll 15 patients.
The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of
3-6 weeks), and a Follow-up Period (visits approximately every 12 weeks for up to 2 years
after treatment discontinuation).
Inclusion Criteria:
1. Male or female patient aged 18 years or older.
2. Pathologic diagnosis of one of the following solid tumor malignancies which is locally
advanced or metastatic at screening:
1. Breast cancer which is ER negative, partial response (PR) negative, and HER2
negative
2. Colorectal cancer
3. Esophageal cancer
4. Gastric cancer
5. Head and neck cancer (squamous cell carcinoma and nasopharyngeal carcinoma)
6. Mesothelioma
7. Non-small cell lung cancer
8. Ovarian cancer
9. Pancreatic cancer
10. Soft Tissue Sarcomas
3. Patients with relapsed or refractory disease who have failed, or are intolerant to,
any established therapy; or for whom no other treatment options are available, in the
opinion of the Investigator.
4. Measurable disease per RECIST 1.1.
5. Patient must agree to biopsy of tumor for study biomarker testing.
6. Eastern Cooperative Oncology Group performance status, 0 to 1.
7. Adequate organ function as defined by screening laboratory values within the following
parameters:
1. Absolute neutrophil count (ANC) ≥ 1.5 × 103/µL (off growth factors at least 72
hours)
2. Platelet count ≥100 x 103/µL without transfusion
3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
glutamyl transferase (GGT) ≤ 2.5 × the upper limit of normal (ULN); ≤ 5 × ULN if
there is liver involvement with tumor
4. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert's syndrome may have a
total bilirubin up to ≤ 3 × ULN)
5. Blood creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min by
the Cockcroft and Gault equation.
8. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior
to start of study drug (C1D1) for women of childbearing potential.
9. Women of childbearing potential must agree to use a highly effective method of
contraception from the time of giving informed consent until at least 16 weeks after
the last dose of ADCT-601. Men with female partners who are of childbearing potential
must agree that they will use a highly effective method of contraception from the time
of giving informed consent until at least 16 weeks after the patient receives his last
dose of ADCT-601.
Exclusion Criteria:
1. Known history of ≥ Grade 3 hypersensitivity to a therapeutic antibody.
2. Active second primary malignancy other than nonmelanoma skin cancers, nonmetastatic
prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the
breast, or other malignancy that the Sponsor's medical monitor and Investigator agree
and document should not be exclusionary.
3. Active autoimmune disease, including motor neuropathy considered of autoimmune origin
and other central nervous system (CNS) autoimmune disease. Patients with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll, provided the trigger can be avoided.
4. Known seropositive and requiring antiviral therapy for human immunodeficiency virus,
hepatitis B virus, or hepatitis C virus.
5. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
6. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or
previously documented cerebrospinal fluid cytology).
Previously treated asymptomatic CNS metastases are permitted provided that the last
treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥ 8
weeks prior to Day 1 except usage of low dose of steroids on a taper (ie, up to 10 mg
on Day 1 and consecutive days is permissible if being tapered down). Patients with
discrete dural metastases are eligible.
7. Clinically significant third space fluid accumulation (ie, ascites requiring drainage
or pleural effusion that is either requiring drainage or associated with shortness of
breath).
8. Breastfeeding or pregnant.
9. Significant medical comorbidities, including but not limited to, uncontrolled
hypertension (blood pressure [BP] ≥ 160/100 mmHg repeatedly), unstable angina,
congestive heart failure (greater than New York Heart Association class II),
electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial
infarction within 6 months prior to screening, uncontrolled atrial or ventricular
cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease.
10. Major surgery, radiotherapy, chemotherapy, or other antineoplastic therapy within 14
days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.
11. Use of any other experimental medication within 14 days prior to start of study drug
(C1D1).
12. Planned live vaccine administration after starting study drug (C1D1).
13. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE]
version 4.0) from acute non-hematologic toxicity (Grade ≤ 2 neuropathy or alopecia)
due to previous therapy prior to screening.
14. Congenital long QT syndrome or a corrected QTcF interval of > 480 ms at screening
(unless secondary to pacemaker or bundle branch block).
15. Any other significant medical illness, abnormality, or condition that would, in the
Investigator's judgment, make the patient inappropriate for study participation or put
the patient at risk.
