Safety, Tolerability, Pharmacokinetics, and Antitumor Study of ADCT-601 to Treat Advanced Solid Tumors

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.