Study of ADCT-502 in Patients With Advanced Solid Tumors Withhuman Epidermal Growth Factor Receptor-2 (HER2) Expression
Condition: Breast Cancer; Non Small Cell Lung Cancer; GastroEsophageal Cancer; Bladder Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms
Intervention: ADCT-502
Intervention description: Intravenous Infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study evaluated ADCT-502 in participants with Advanced Solid Tumors with HER2
      Expression. Participants participated in a dose-escalation phase (Part 1) and were due to
      participate in the dose expansion phase (Part 2). In Part 2, patients were due to receive the
      dose level identified in Part 1, but the study was terminated prior to the beginning of Part
      2.
    

Eligibility criteria:

        Main Inclusion Criteria:

          -  Male or female age 18 years or older

          -  Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit
             for their condition.

          -  Eastern Cooperative Oncology Group (ECOG) performance status: Part 1: 0-2, Part 2: 0-1

          -  Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or
             unstained slides to demonstrate HER2 expression.

          -  Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic
             at time of Screening with documented HER2 expression.

          -  Part 2/Dose Expansion Only: Measurable disease as defined by Response Evaluation
             Criteria in Solid Tumors (RECIST) version 1.1

          -  Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥1.5× 109/L).

          -  Platelet count ≥100,000 //mm3 (≥100 × 109/L).

          -  Hemoglobin ≥ 9 g/L (≥5.6 mmol/L).

          -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of
             normal (ULN); or ≤ 5.0 × ULN if liver metastases are present.

          -  Total bilirubin ≤ 1.5× ULN (or ≤ 3× ULN, with direct bilirubin ≤1.5 × ULN, in
             participants with known Gilbert syndrome).

          -  Creatinine ≤ 1.5× ULN; or, if serum creatinine > 1.5 × ULN, a measured creatinine
             clearance must be >60mL/min/1.73m2 as calculated by the Cockcroft and Gault equation
             for participants to be eligible.

          -  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-502. Men with female partners who are of childbearing potential
             must agree that they or their partners will use a highly effective method of
             contraception from the time of giving informed consent until at least 16 weeks after
             the participant receives his last dose of ADCT-502.

        Main Exclusion Criteria:

          -  Known history of ≥ Grade 3 hypersensitivity to a therapeutic antibody.

          -  Known history of positive serum human anti-drug antibody (ADA) to trastuzumab.

          -  Major surgical procedure or significant traumatic injury, radiotherapy, chemotherapy,
             targeted therapy, hormone therapy, or other anticancer therapy.

          -  Failure to recover to Grade 0 or Grade 1 from acute non-hematologic toxicity due to
             previous therapy, prior to screening (with the exception of alopecia).

          -  Central Nervous System (CNS) disease only.

          -  Symptomatic CNS metastases or evidence of leptomeningeal disease.

          -  Active cardiovascular disease or significant history thereof.

          -  Other active disease including but not limited to ulceration of the upper
             gastrointestinal tract, autoimmune disease, HIV infection, active Hepatitis B virus
             (HBV) and hepatitis C virus (HCV) infection.

          -  Breastfeeding or pregnant.

          -  Other concurrent severe and/or uncontrolled medical conditions.