SGNLVA-002: Single arm, open label, phase Ib/II study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer
Authors: V. Boni, C. Alemany, J.L. Meisel, R. Sinha, D. Sterrenberg, K.H.R. Tkaczuk, Y. Wang, Z. Wang, H.S. Han
Journal: Annals of Oncology (2019)

Background: Patients with metastatic triple negative breast cancer (mTNBC) subtype have poor outcomes with a median overall survival (OS) of approximately 1 year. SGN-LIV1A, or ladiratuzumab vedotin (LV), is an investigational monomethyl auristatin E (MMAE)-conjugated humanized IgG1 antibody-drug conjugate (ADC) against LIV-1, a highly expressed transmembrane protein in breast cancer cells. LV mediated delivery of MMAE drives antitumor activity through cytotoxic cell killing and has been shown to induce immunogenic cell death (ICD). Preliminary results from an ongoing phase 1 study show that LV monotherapy is well tolerated and has encouraging antitumor activity in patients with mTNBC. Pembrolizumab, a checkpoint inhibitor that elicits antitumor activity by targeting the T cell inhibition pathway, showed limited response in the treatment of locally advanced/metastatic (LA/M) TNBC as monotherapy. Combining LV and pembrolizumab may result in synergistic activity through LV-induced ICD that creates a microenviroment favorable for enhanced anti-programmed cell death protein 1 activity. Trial design: SGNLVA-002 is a single-arm, open label Phase 1b/2 study of LV in combination with pembrolizumab as first line therapy for patients with LA/M TNBC (CT.gov: NCT03310957 EudraCT: 2017-002289-35). This study consists of 2 parts: dose finding and dose expansion, which are enrolling sequentially. Patients must not have had prior cytotoxic or anti-PD(L)1 treatment for advanced disease. Patients must have measureable disease per RECIST v1.1 and an ECOG score of 0 or 1. The dose finding phase was a dose de-escalation study and started at 2.5 mg/kg LV + 200 mg pembrolizumab every three weeks. The primary objective is to assess the safety/tolerability of LV+pembrolizumab, identify the recommended phase 2 dose of LV, and evaluate ORR by RECIST v1.1. The secondary objectives include evaluation of DOR, DCR, PFS, and OS. The first patient was enrolled in March 2018 and the study is currently enrolling in the US and EU. Editorial acknowledgement: Wendi Schultz and Amy Mackay, Seattle Genetics, Inc. Clinical trial identification: NCT03310957 EudraCT: 2017-002289-35. Legal entity responsible for the study: Seattle Genetics Inc. Funding: Seattle Genetics, Inc. Disclosure: V. Boni: Research funding: Seattle Genetics, Inc.; Advisory board membership: Loxo Therapeutics, Ideya; Corporate board membership: ASCO, ESMO, SEOM, SOLTI. C. Alemany: Research funding: Seattle Genetics, Inc.; Speaker's bureau: Alexion Pharmaceuticals, Inc. J.L. Meisel: Research funding: Seattle Genetics, Inc.; Consultancy: Puma, Pfizer; Honoraria: Total Health Conferencing; Travel expenses: Puma, Pfizer, Total Health Conferencing (travel to meetings). R. Sinha: Research funding: Seattle Genetics, Inc. D. Sterrenberg: Research funding: Seattle Genetics, Inc.; Speaker's bureau: Puma Biotechnology, Tesaro. K.H.R. Tkaczuk: Grant info: Institutional grant support: Seattle Genetics, Inc.; Research funding grants, institutional grant support: Seattle Genetics, Inc. Y. Wang, Z. Wang: Employment, equity ownership: Seattle Genetics, Inc. H.S. Han: Research funding grants: Pfizer, Abbvie, TapImmune, G1 Therapeutics, Horizon, BMS, Novartis, Tesaro, Seattle Genetics, Inc.; Grant info: Department of Defense; Travel expenses: Pfizer.