357TiP SGNLVA-002: Single arm, open-label, phase Ib/II study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of triple-negative breast cancer

Abstract

Patients (pts) with metastatic triple-negative breast cancer (mTNBC) have a poor prognosis. Treatment combinations of anti-programmed death (ligand) 1 [anti-PD(L)1] agents with chemotherapy have shown promise in mTNBC. LIV-1 is a transmembrane protein highly expressed on breast cancer cells. SGN-LIV1A, or ladiratuzumab vedotin (LV), is an investigational antibody-drug conjugate that combines a humanized anti-LIV-1 IgG1 monoclonal antibody with the microtubule-disrupting agent, monomethyl auristatin E (MMAE) via a protease-cleavable linker. LIV-1 mediated delivery of MMAE disrupts microtubules and induces cell cycle arrest and apoptosis. Additionally, LV has been shown to drive immunogenic cell death (ICD) to elicit an immune response. Combining LV and pembrolizumab may result in synergistic activity through LV induced ICD that creates a microenvironment favorable for enhanced anti-PD(L)1 activity. Preliminary results of LV delivered once every 3 weeks with pembrolizumab was shown to be tolerable with encouraging antitumor activity in pts with mTNBC (SABCS 2019). In order to enhance efficacy and improve the tolerability profile, LV delivered weekly with pembrolizumab is being evaluated. SGNLVA-002 is a global single-arm, open-label phase Ib/II study of LV with pembrolizumab as first-line therapy for pts with unresectable locally-advanced or mTNBC. The study is currently enrolling approximately 24 pts to evaluate the safety and efficacy of LV at either 1.00 or 1.25 mg/kg/week on Days 1, 8, and 15 plus pembrolizumab 200 mg on Day 1 of each 21 day cycle. Pts must not have had prior cytotoxic or anti-PD(L)1 treatment for advanced disease, have measurable disease per RECIST v1.1, and an ECOG score of 0 or 1. The primary objectives are to evaluate the safety/tolerability and objective response rate of weekly LV plus pembrolizumab, and to identify the recommended phase II dose and schedule of weekly LV in combination with pembrolizumab. The secondary objectives include evaluation of duration of response, disease control rate, progression-free survival, and overall survival. Study enrollment is ongoing in the US, Asia, and EU. Medical writing assistance was funded by Seattle Genetics, Inc., and provided by William Losin of MMS Holdings, Inc. Seattle Genetics/Merck.