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Abstract
Background Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Recently, the introduction of immunotherapy has improved outcomes in the frontline treatment of recurrent/metastatic (r/m) HNSCC, though clinical outcomes can be further optimized. For patients with disease progression after prior immunotherapy and platinum-based chemotherapy, there remains a large unmet need for novel therapies. Tisotumab vedotin (TV) is a tissue factor-directed antibody-drug conjugate (ADC) currently being investigated in multiple solid tumors. Preclinical data suggest that vedotin-based ADCs, including TV, may induce cancer cell apoptosis in a manner consistent with immunogenic tumor cell death, providing a rationale for combining TV with immune checkpoint inhibitors.1 A recent study evaluating the combination of TV with other therapeutics, including immune checkpoint inhibitors, has shown promising data in cervical cancer.2 Furthermore, in patients with r/m HNSCC with disease progression after prior platinum combination and immunotherapy, TV has shown encouraging antitumor activity.3 Here, we present the newly added cohorts from innovaTV 207 (NCT03485209) in patients with r/m HNSCC.
Methods innovaTV 207 is an open label, phase 2, multicenter study evaluating TV monotherapy or in combination for advanced solid tumors (figure 1). In the newly added Parts E and F, presented herein, only patients with r/m HNSCC will be enrolled.
In Part E, eligible patients with HNSCC must have experienced disease progression on or after their most recent systemic therapy including platinum-based chemotherapy and immunotherapy. Patients could have received no more than 2 lines of systemic therapy in the r/m setting. TV monotherapy will be administered at 1.7 mg/kg IV on Days 1 and 15 of a 28-day cycle (Q2W). The primary endpoint is confirmed ORR by BICR, as measured by RECIST v1.1.
In Part F, eligible patients with r/m HNSCC cannot have received any previous systemic therapy for r/m disease and must have a tumor CPS ≥1 by local PD-L1 testing. TV will be administered at 1.7 mg/kg IV Q2W in combination with pembrolizumab 400 mg IV Q6W. The primary endpoint is confirmed ORR by investigator, as measured by RECIST v1.1.
Secondary endpoints for Parts E and F include safety, tolerability, DCR, DOR, TTR, and OS. Enrollment for innovaTV 207 Parts E and F is currently open.
Acknowledgements This study was funded by Genmab (Copenhagen, Denmark) and Seagen Inc. (Bothell, WA, USA). Tisotumab vedotin is being co-developed by Genmab and Seagen Inc.
Jennifer Yang, PhD, of Seagen Inc. provided medical writing and editorial support with funding from Seagen Inc., in accordance with Good Publication Practice guidelines.
Trial Registration Clinicaltrials.gov: NCT03485209
References
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Ethics Approval The trial is being conducted in compliance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice. All patients, or their legal representatives, provided informed consent. All participating sites have been approved by a corresponding institutional review board or independent ethical committee per the participating institution.
BICR, blinded independent central reviews; CPS, combined positive score; DCR, disease control rate; DOR, duration of response; HNSCC, head and neck squamous cell carcinoma; ORR, objective response rate; OS, overall survival; PD-L1; programmed cell death protein liga nd-1; PFS, progression-free survival; Q2W, once every 2 weeks; Q6W, once every 6 weeks; RECIST v1.1, Response Criteria in Solid Tumors Version 1.1; r/m, recurrent or metastatic; SMC, Safety Monitoring committee
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