A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)

The study objectives are to evaluate the safety, antitumor activity, and pharmacokinetics of tisotumab vedotin (TV) administered every 3 weeks or on Days 1, 8, and 15 of every 4-week cycle (3Q4W) for patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has relapsed within 6 months of the completion of platinum-based treatment and determined to be platinum resistant. All patients must have PROC and be eligible for single agent chemotherapy.

The safety run-in period will evaluate the safety of a weekly schedule. The highest dose level that is considered safe will be the recommended phase 2 dose (RP2D) and will be used in Part A. In Part A, participants will be randomized in a 1:1 ratio to receive tisotumab vedotin intravenously (IV) every 3 weeks (Q3W regimen) or the safety run-in RP2D on Days 1, 8, and 15 of every 4-week cycle (weekly regimen; 3Q4W) if a RP2D has been identified. Participants who enroll in Part B will receive tisotumab vedotin on Days 1, 8, and 15 of every 4-week cycle (weekly regimen) at a pre-specified dose level, if the dose level is considered safe and tolerable in the safety run-in period.

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