Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

Clinical trial: Study of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression

Summary: This study evaluates ADCT-502 in patients with Advanced Solid Tumors with HER2 Expression. Patients will participate in a dose-escalation phase (Part 1) and dose expansion (Part 2). In Part 2, patients will receive the dose level identified in Part 1.

Detailed description: Study ADCT-502-101 is the first clinical study with ADCT-502 in patients with Advanced Solid Tumors with HER2 Expression.
  ADCT-502 is an antibody drug conjugate (ADC) composed of an engineered version of the humanized monoclonal antibody trastuzumab, directed against the human HER2 receptor, conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. ADCT-502 specifically binds to HER2, and once internalized, releases the PBD dimer to allow cross-linking of DNA and eventually trigger cell death.
  The study will be conducted in 2 parts. In Part 1 (dose escalation) patients will receive an infusion of ADCT-502, at escalating doses. Part 1 will continue until the maximum tolerated dose or the recommended dose(s) and schedule(s) for expansion are determined. In Part 2 (expansion), patients will be assigned to the recommended dose level of ADCT-502 identified in Part 1 by the 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 weeks 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 as patients may continue treatment until disease progression or unacceptable toxicity. It is anticipated that the duration of the entire study (Parts 1 and 2) could be approximately 3 years from first patient treated to last patient completed.

Eligibility: 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 patients 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 patient 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 patient 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 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 HBV and HCV infection.
  -  Breastfeeding or pregnant.
  -  Other concurrent severe and/or uncontrolled medical conditions.

Relevance to patient case: possibly relevant