1064TiPPhase I/II trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)

Abstract Background The current standard-of-care first-line therapy for patients (pts) with recurrent/metastatic cervical cancer (r/mCC) is paclitaxel/platinum ± bevacizumab (BEV). However, approximately 50% of pts who are eligible to receive this regimen do not respond to the treatment. Tissue factor (TF) is highly expressed in cervical cancer and is associated with poor prognosis. Tisotumab vedotin (TV) is an investigational first-in-class antibody-drug conjugate comprising a fully human monoclonal antibody targeting TF conjugated to the microtubule-disrupting agent monomethyl auristatin E via a protease-cleavable linker. Single-agent TV demonstrated encouraging antitumor activity (independent review committee–assessed confirmed ORR, 22%; median DOR, 6.0 mo) and a manageable safety profile in pts with previously treated r/mCC. innovaTV 205/ENGOT-cx8 (NCT03786081; GOG-3024) is a global, multicenter, open-label, phase 1/2 trial evaluating the safety and antitumor activity of TV in combination with BEV, pembrolizumab (PEM), or carboplatin (CBP) in pts with untreated and previously treated r/mCC. Results from the innovaTV 205 study will inform the further clinical development of TV in cervical cancer. Trial design Approximately 140 adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix; measurable disease; and ECOG PS 0-1 will be enrolled. The phase 1 portion of the study will consist of 3 dose escalation cohorts for identification of the recommended phase 2 dose (RP2D) of TV with BEV, PEM, or CBP. The phase 2 portion will include 3 expansion cohorts. In the dose escalation cohorts, previously treated pts will receive escalating doses of TV (IV 1Q3W) in combination with escalating doses of BEV (IV 1Q3W), a fixed dose of PEM (IV 1Q3W), or a fixed dose of CBP (IV 1Q3W). In the expansion cohorts, pts who have not received prior systemic therapy for r/mCC will receive 1) TV RP2D + PEM or 2) TV RP2D + CBP; pts who received 1-2 prior treatments for r/mCC will receive TV RP2D + PEM. Additional cohorts might be added. The primary endpoint of phase 2 is ORR (RECIST v1.1). Secondary endpoints include DOR, time to response, PFS, OS, and safety. Clinical trial identification NCT03786081; GOG-3024. Editorial acknowledgement ApotheCom, San Francisco, CA, USA. Legal entity responsible for the study Genmab. Funding Genmab. Disclosure I.B. Vergote: Advisory / Consultancy: Advaxis; Advisory / Consultancy: Eisai; Advisory / Consultancy: