Abstract 882TiP
Background
Platinum-resistant ovarian cancer (PROC), defined as progression within 6 months from completion of platinum-containing therapy, is associated with poor prognosis. Tissue Factor (TF) is a novel target highly expressed in several solid tumors including ovarian cancer. Tisotumab vedotin (TV) is an investigational antibody-drug conjugate designed to bind to TF on target cells and to release monomethyl auristatin E (MMAE), a microtubule-disrupting agent, upon internalization resulting in cell cycle arrest and apoptotic cell death. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase I/II innovaTV 201 trial. The innovaTV 208 trial is a multicenter, open-label, phase II trial evaluating the efficacy and safety of TV given on a dosing schedule of every 3 weeks (Q3W) or on days 1, 8, and 15 of a 28-day cycle (weekly) in patients with PROC. This abstract presents the newly added Part B of the expansion phase, investigating the IV administration of TV (0.9 mg/kg) on the weekly dosing schedule.
Trial design
The innovaTV 208 trial consists of a safety run-in followed by a multipart dose expansion phase composed of a randomized comparison of 3Q4W and weekly dosing (Part A) and a newly added cohort (Part B). Part B will enroll ∼40 adult women with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; ECOG score 0 to 1, and who are eligible for single agent chemotherapy. Exclusion criteria include women with primary platinum refractory disease, increased risk of bleeding, active ocular surface disease, or Grade ≥2 peripheral neuropathy. Patients who have received at most 1 prior cytotoxic chemotherapy treatment regimen in the PROC setting, will receive TV on Days 1, 8, and 15 of a 28-day cycle at 0.9 mg/kg IV. The primary endpoint for the dose expansion phase is confirmed ORR by RECIST v1.1 as assessed by the investigator. Secondary endpoints include duration of response, disease control rate, time to response, progression-free survival, overall survival, Cancer Antigen 125 (CA-125) response rate, pharmacokinetic profile, and safety. The ongoing trial opened in March 2019 and was amended to add Part B in October 2019.
Clinical trial identification
NCT03657043.
Editorial acknowledgement
Medical Writing support was funded by Seattle Genetics, Inc., and provided by Suzanne Canada of ExecuPharm.
Legal entity responsible for the study
Genmab A/S and Seattle Genetics, Inc.
Funding
Genmab A/S and Seattle Genetics, Inc.
Disclosure
S. Blank: Advisory/Consultancy, Research grant/Funding (institution), steering committee on study (GOG 3015): Roche; Advisory/Consultancy, DSMB: Aravive; Leadership role, Travel/Accommodation/Expenses, Officer/Board of Directors: SGO; Leadership role, Travel/Accommodation/Expenses, Officer/Board of Directors: ABOG; Leadership role, Travel/Accommodation/Expenses: ACOG; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Tesaro/GSK; Research grant/Funding (institution): AstraZeneca; Shareholder/Stockholder/Stock options: Johnson and Johnson; Full/Part-time employment: Icahn School of Medicine at Mount Sinai; Officer/Board of Directors: SHARE; Officer/Board of Directors: NOCC. O. Tehrani: Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Seattle Genetics. S. Ghamande: Honoraria (self), Speaker Bureau/Expert testimony: Tesaro/GSK; Research grant/Funding (institution): Merck; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Takedo; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): BMS. S. Jain: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. L. Nicacio: Shareholder/Stockholder/Stock options: Florence Healthcare; Honoraria (institution), Travel/Accommodation/Expenses, Full/Part-time employment: Seattle Genetics. I. Soumaoro: Full/Part-time employment: Genmab. D.M. O'Malley: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Immunogen; Advisory/Consultancy: Ambry; Advisory/Consultancy, Research grant/Funding (institution): Janssen/J&J; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Novocure; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): VentiRx; Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Ergomed; Research grant/Funding (institution): Ajinomoto Inc.; Research grant/Funding (institution): Ludwig Cancer Research; Research grant/Funding (institution): Stemcentrx, Inc; Research grant/Funding (institution): Cerulean Pharma; Advisory/Consultancy, Research grant/Funding (institution): GOG Foundation; Research grant/Funding (institution): Bristol-Myers Squibb Co; Research grant/Funding (institution): Serono Inc; Research grant/Funding (institution): Tracon Pharmaceuticals; Research grant/Funding (institution): Yale University; Research grant/Funding (institution): New Mexico Cancer Care Alliance; Research grant/Funding (institution): INC Research, Inc; Research grant/Funding (institution): inVentiv Health Clinical; Research grant/Funding (institution): Iovance Biotherapeutics; Research grant/Funding (institution): PRA Intl; Advisory/Consultancy: Myriad Genetics; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Agenus; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Tarveda; Advisory/Consultancy, Research grant/Funding (institution): Merck. All other authors have declared no conflicts of interest.