Efficacy and Safety of Tisotumab Vedotin in Patients with Head and Neck Squamous Cell Carcinoma: Results From a Phase II Cohort

Abstract

<h3>Purpose/Objective(s)</h3> Tisotumab vedotin (TV) is an antibody-drug conjugate directed against tissue factor, which is highly prevalent in some solid tumors. In Sep 2021, the US FDA approved TV monotherapy for recurrent or metastatic cervical cancer (r/mCC) patients with disease progression on or after chemotherapy. Encouraging early data from investigational TV combinations with carboplatin and pembrolizumab in relapsed cervical cancer suggest that these combinations may have activity in other cancers (Vergote 2021). innovaTV 207 evaluated TV in solid tumors, including a cohort of squamous cell carcinoma of the head and neck (SCCHN). We report the clinical activity and safety of TV 2 mg/kg Q3W in this cohort. <h3>Materials/Methods</h3> In this global, open label, phase 2, multicenter study, SCCHN cohort patients received 2 mg/kg TV (max dose: 200 mg per infusion) IV on Day 1 of each 21-day cycle. Eligible patients had: 1) relapsed, locally advanced, or metastatic SCCHN, and experienced disease progression on or after their most recent systemic therapy, 2) received prior therapy with a platinum-based regimen and a checkpoint inhibitor (if eligible), 3) received anti-epithelial growth factor receptor therapy prior to study entry (if eligible), and 4) received no more than 3 systemic regimens in the recurrent/metastatic setting. The primary endpoint was investigator confirmed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and tolerability. <h3>Results</h3> Of 31 SCCHN patients enrolled, median age was 65.0 (range 47-78) years. As of 15 Oct 2020, median duration of ongoing TV therapy was 12.0 weeks (range 3-36). Confirmed ORR was 16% (95% CI: 5.5-33.7); 5 patients had a partial response. Confirmed DCR was 58.1% (95% CI: 39.1-75.5). Median PFS was 4.2 months (95% CI: 2.7–4.8), and median OS was 9.4 months (95% CI: 8.1-11.8). Twenty-two (71.0%) patients developed Grade ≥3 treatment-emergent adverse events (TEAEs); most commonly (≥10% of patients) anemia (16.1%), pneumonia (12.9%), and dyspnea (12.9%). Reported incidence for all grade TEAEs of special interest for ocular, bleeding, and peripheral neuropathy events was 54.8%, 51.6%, and 29.0%, respectively. Incidence of treatment-emergent serious adverse events (SAEs) was 51.6%, and treatment related SAEs was 6.5% (grade 3 hemoptysis [n=1] and grade 3 post procedural hemorrhage [n=1]). There were 2 adverse events leading to death (aspiration and pulmonary embolism); none were considered treatment related. <h3>Conclusion</h3> TV has a manageable safety profile and favorable preliminary antitumor activity in patients with SCCHN that have progressed after a platinum containing regimen and a checkpoint inhibitor. Continued evaluation of TV is warranted. This trial is ongoing and is registered with ClinicalTrials.gov (NCT03485209).