SGNTV-001: Open label phase 2 study of tisotumab vedotin for locally advanced or metastatic disease in solid tumors.

Abstract

TPS3160 Background: Tisotumab vedotin (TV) is being developed for patients with cervical cancer and other solid tumors known to express Tissue Factor (TF). Expression of TF on tumor cells has been associated with poor prognosis in several tumor types. Four tumor types were chosen for this study based on unmet medical need and TF expression. TV is an antibody-drug conjugate composed of a TF-targeted fully human monoclonal immunoglobulin G1 conjugated via a protease-cleavable valine citrulline linker to the drug monomethyl auristatin E (MMAE). TV-mediated delivery of MMAE drives antitumor activity through cytotoxic cell killing and has been shown to induce immunogenic cell death (ICD). In preclinical studies, TV treatment resulted in potent and long-lasting tumor regression in TF-expressing xenograft models derived from a variety of solid cancers, including patient-derived xenograft models with heterogeneous TF expression. TV has shown preliminary evidence of activity in heavily pretreated patients with many TF-expressing tumor types in the GEN701 phase 1 study. Methods: SGNTV-001 (innovaTV 207) is a global, open label, multicenter phase 2 trial designed to assess the safety, tolerability, and activity of TV for the treatment of solid tumors. (NCT03485209; EudraCT 2017-005076-26). Patients are currently enrolling in 4 cohorts: colorectal cancer (CRC), squamous non-small cell lung cancer (NSCLC), exocrine pancreatic adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN). Patients must have measureable disease per RECIST v1.1 that has progressed despite standard of care systemic treatment in the locally advanced or metastatic setting (up to 3 prior lines for CRC, 2 for squamous NSCLC and SCCHN, and 1 for pancreatic adenocarcinoma) and have an ECOG score of 0 or 1. The primary endpoint is investigator-determined confirmed ORR as measured by RECIST v1.1. Secondary objectives include DOR, PFS, OS, DCR, and TTR, as well as safety and pharmacokinetic parameters. The first patient was enrolled in July 2018 and the study is currently enrolling across 16 sites in the US (as of January 2019) with additional sites opening in EU countries. Clinical trial information: NCT03485209.