A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)
Condition: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: tisotumab vedotin
Intervention description: Intravenous (IV) infusion
Intervention MeSH terms: Tisotumab vedotin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 98.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Platinum-resistant; Antibody drug conjugate; Tisotumab vedotin; PROC; Seattle Genetics

Summary:

      This trial will study tisotumab vedotin to find out what its side effects are and to see if
      it works for platinum-resistant ovarian cancer (PROC). It will test different doses of
      tisotumab vedotin that are given at different times. It will also compare the side effects
      and ability to treat tumors of these different doses and schedules. In this study, there will
      be a safety run-in group of approximately 12 patients that will look at a dose-dense
      treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In
      addition to the safety run-in patients, there will be three groups in the study. One group
      will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get
      tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or
             fallopian tube cancer

          -  Safety run-in only: PROC. Patients may have received more than 1 prior systemic
             treatment regimen in the PROC setting.

          -  Part A and Part B only: Patients with PROC who have received 1 to 3 anticancer lines
             of therapy overall, including at least 1 line of therapy containing bevacizumab or
             biosimilar.

               -  Adjuvant ± neoadjuvant are considered 1 line of therapy.

               -  Patients may have received a PARP inhibitor or an immuno-oncology (IO) agent; any
                  of these regimens are to be considered a line of therapy for the purposes of this
                  study if not used as maintenance therapy.

               -  Maintenance therapy (including bevacizumab, PARP inhibitors and IOs) will be
                  considered part of the preceding line of therapy and not to be counted as a new
                  line of therapy.

               -  Any chemotherapy regimen change due to toxicity in the absence of disease
                  progression is considered as part of the same line of therapy.

               -  Hormonal therapy will be not be counted towards the lines of therapy.

          -  Measurable disease according to RECIST v1.1 as assessed by the investigator

          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

          -  Life expectancy of at least 3 months

          -  Able to provide fresh or archival tissue for biomarker analysis

        Exclusion Criteria:

          -  Primary platinum-refractory disease, defined as disease progression within 2 months of
             completion of first line platinum-based therapy

          -  Patients with clinical symptoms or signs of gastrointestinal obstruction with the past
             6 months or who currently require parenteral nutrition

          -  Hematological: Known past or current coagulation defects leading to an increased risk
             of bleeding, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis,
             ongoing major bleeding, or trauma with increased risk of life-threatening bleeding
             within 8 weeks of trial entry

          -  Cardiovascular: Clinically significant cardiac disease including uncontrolled
             hypertension, unstable angina, acute myocardial infarction with 6 months of screening,
             serious cardiac arrhythmia requiring medication, medical history of congestive heart
             failure, or medical history of decreased cardiac ejection fraction of <45%

          -  Ophthalmological: Active ocular surface disease at baseline or prior episode of
             cicatricial conjunctivitis or Stevens Johnson syndrome

          -  Prior treatment with MMAE-derived drugs

          -  Inflammatory bowel disease including Crohn's disease and ulcerative colitis

          -  Ongoing, acute, or chronic inflammatory skin disease

          -  Uncontrolled tumor-related pain

          -  Inflammatory lung disease requiring chronic medical therapy

          -  Grade 3 or higher pulmonary disease unrelated to underlying malignancy

          -  Uncontrolled pleural or pericardial effusions

          -  Grade >1 peripheral neuropathy

          -  Patients who are pregnant or breastfeeding