Abstract CT164: Tisotumab vedotin (TV) in squamous cell carcinoma of head and neck (SCCHN): interim analysis from innovaTV 207
Authors: Cirauqui Beatriz , Salas Sebastien , William William , Birnbaum Ariel E. , Schmidt Kristi , Guan Xuesong , Soumaoro Ibrahima , Nicacio Leonardo , Ciardiello Fortunato 
Published: April 2023

Abstract
Introduction: TV, a tissue factor (TF)-directed antibody-drug conjugate, is approved under accelerated approval in the US at a dose of 2.0 mg/kg IV administered every 3 weeks (Q3W) for adult patients (pts) with recurrent or metastatic (r/m) cervical cancer who have progressed on or after chemotherapy. TV is also being evaluated in several advanced solid tumors known to express TF, including SCCHN; antitumor activity has been observed at the approved dose level. Previous reports show that modifying the dosing schedule to optimize key PK parameters such as AUC, Cmax, and Ctrough can lead to further improvement in clinical efficacy. A population PK model based on 399 pts across clinical trials suggests that when TV is administered at 1.7 mg/kg IV on Days 1 and 15 of a 28-day cycle (Q2W), pts are predicted to achieve 24% higher AUC, a higher Ctrough level, and a lower Cmax, compared with the approved cervical cancer regimen (2.0 mg/kg Q3W). Here, we report the first analysis of TV 1.7mg/kg Q2W for r/m SCCHN that has progressed after prior platinum combination with or without immunotherapy.
Methods: innovaTV 207 (NCT03485209) is an open label phase 2 multi-center study evaluating TV monotherapy or in combination for advanced tumors, including pts with r/m SCCHN. In Part C of the study, eligible pts could have received up to 3 lines of systemic therapy for r/m disease and must have received prior therapy with a platinum-based regimen and a checkpoint inhibitor (CPI), if eligible. TV was administered at 1.7 mg/kg IV Q2W. The primary endpoint was objective response rate (ORR), and secondary endpoints included safety and tolerability.
Results: At data cutoff (28Nov2022), 15 pts with SCCHN were treated. The median number of prior lines for r/m disease was 2. All pts received prior platinum therapy and majority (93%) received a CPI. 67% of pts received cetuximab and 53% received taxanes, for r/m SCCHN. Confirmed ORR was 40% (95% CI: 16.3, 67.7), with 1 complete response and 5 partial responses. The safety profile was generally consistent with that observed across TV monotherapy clinical studies. 13 pts experienced a treatment-related adverse event (TRAE), most commonly asthenia (n=7), peripheral sensory neuropathy (PSN) (n=7), and vomiting (n=5). 4 pts experienced Grade ≥3 TRAEs. 2 pts discontinued treatment due to an AE (PSN and dry eye, n=1 each). 11 pts received 3 or more cycles of treatment (1 cycle = 28 days).
Conclusions: For pts with r/m SCCHN who have progressed after prior platinum combination and immunotherapy, TV may be a promising treatment option. Preliminary data suggest encouraging antitumor activity at a higher exposure with Q2W administration while maintaining an acceptable safety profile. The innovaTV 207 study is still enrolling and different dosing regimens are currently being evaluated across advanced solid tumors.
Citation Format: Beatriz Cirauqui, Sebastien Salas, William William, Ariel E. Birnbaum, Kristi Schmidt, Xuesong Guan, Ibrahima Soumaoro, Leonardo Nicacio, Fortunato Ciardiello. Tisotumab vedotin (TV) in squamous cell carcinoma of head and neck (SCCHN): interim analysis from innovaTV 207 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT164.