Abstract

5531 Background: Tisotumab vedotin (TV) is an antibody-drug-conjugate directed to tissue factor with a microtubule-disrupting agent, MMAE, payload. The ENGOT-cx12/GOG-3057/innovaTV study 301 (NCT04697628) was the first to report OS benefit for TV vs chemotherapy in 2L/3L recurrent or metastatic cervical cancer (r/mCC), including in pts who have received prior anti-PD-(L)1 (HR 0.70; Vergote, Ann Oncol 2023). This abstract presents additional data on the use of subsequent therapies in this study. Methods: innovaTV 301 is a global, randomized, open-label phase 3 study. Eligible pts had r/mCC with disease progression on/after chemotherapy doublet ± bevacizumab and an anti-PD-(L)1 agent, if eligible and available. Pts were randomized 1:1 to TV monotherapy (2.0 mg/kg Q3W) or investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). Primary endpoint was OS. Descriptive analyses on type and time to first subsequent anticancer therapy are reported. Results: 502 pts were randomized (TV: 253; chemotherapy: 249). All pts received prior systemic therapy; 63.9% of pts had prior bevacizumab and 27.5% of pts had prior anti-PD-(L)1. Observed OS and PFS benefits for TV vs chemotherapy were generally consistent in prespecified subgroups, notably regardless of prior exposure to anti-PD-(L)1. In the ITT population, ORR was 17.8% (95% CI, 13.3-23.1) vs 5.2% (95% CI, 2.8-8.8) and DCR was 75.9% (95% CI, 70.1-81.0) vs 58.2% (95% CI, 51.8-64.4) in the TV vs chemotherapy arms, respectively. Median time-to-response was 1.58 mo and 1.74 mo in the TV and chemotherapy arms, respectively. Following discontinuation of study treatment, 127 (50.2%) pts on the TV arm and 108 (43.4%) on the chemotherapy arm received subsequent anticancer therapy, of which the majority received systemic therapy for progressive disease, including 112 (88.2%) pts on the TV arm and 91 (84.3%) pts on the chemotherapy arm. Median time from last dose of study treatment to first subsequent therapy was 6.7 weeks (range: 1-35) for pts treated with TV and 5.4 weeks (range: 1-51) for pts treated with chemotherapy. The most common types of subsequent systemic therapies were cytotoxic chemotherapy (82/112 [73.2%] vs 57/91 [62.2%] on the TV and chemotherapy arms, respectively) and immunotherapy (42/112 [37.5%] and 32/91 [35.2%] on the TV and chemotherapy arms, respectively). Conclusions: TV previously demonstrated a significant improvement in OS vs chemotherapy that was generally consistent across prespecified subgroups. Additionally, a meaningful proportion of pts received subsequent anticancer therapy in both treatment arms, with cytotoxic chemotherapy and immunotherapy as the most common choices. These data show that TV provides meaningful clinical benefit and does not prevent pts from receiving subsequent therapies, including immunotherapy. Clinical trial information: NCT04697628 .