Abstract 357TiP
Background
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.
Trial design
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.
Clinical trial identification
Editorial acknowledgement
Medical writing assistance was funded by Seattle Genetics, Inc., and provided by William Losin of MMS Holdings, Inc.
Legal entity responsible for the study
Seattle Genetics/Merck.
Funding
Seattle Genetics/Merck.
Disclosure
J. Cortés: Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (institution), Advisory/Consultancy: Lilly; Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Samsung Bioepis; Research grant/Funding (institution): Ariad pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer healthcare; Research grant/Funding (institution): F.Hoffman-La Roche; Research grant/Funding (institution): Guardanth health; Research grant/Funding (institution): Piqur Therapeutics; Research grant/Funding (institution): Puma C; Research grant/Funding (institution): Queen Mary University of London; Shareholder/Stockholder/Stock options: MedSIR. S. Diab: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Agendia; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Genomic Health; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy: Myriad Genetics; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Puma Biotech; Full/Part-time employment: US Oncology Denver; Shareholder/Stockholder/Stock options: Conatus; Shareholder/Stockholder/Stock options: Immunigen; Shareholder/Stockholder/Stock options: Immunomedics; Shareholder/Stockholder/Stock options: Novocure; Shareholder/Stockholder/Stock options: Viking Medical; Honoraria (self): AstraZeneca; Research grant/Funding (self): Seattle Genetics; Travel/Accommodation/Expenses: Genentech. R.K. Basho: Honoraria (self), Speaker Bureau/Expert testimony: Genentech; Advisory/Consultancy: Genomic Health; Research grant/Funding (institution): Seattle Genetics. M. Oliveira: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): PUMA Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Philips Healthcare; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Zenith; Research grant/Funding (institution): Epigenetics; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharma; Travel/Accommodation/Expenses: Grünenthal ; Travel/Accommodation/Expenses: Eisai. T. Pluard: Advisory/Consultancy, Speaker Bureau/Expert testimony: Immunomedics; Advisory/Consultancy: Macrogenics; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony: Tempus; Speaker Bureau/Expert testimony: Genentech; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): H3Bioscience; Research grant/Funding (institution): Daiichi/AstraZeneca; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): GSK; Research grant/Funding (institution): CytoDyn. C. Alemany: Research grant/Funding (institution): Merck Pharmaceuticals; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Janssen Pharmaceuticals; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): Takeda Pharmaceuticals; Research grant/Funding (institution): Celgene Corporation. U. Brown-Glaberman: Advisory/Consultancy: Biotheranostics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Syndax; Advisory/Consultancy: Novartis; Advisory/Consultancy: Halozyme. J. Meisel: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Puma; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Seattle Genetics. J. Ettl: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Teva; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy: PierreFabre; Advisory/Consultancy: Daiichi Sankyo. S. Kuemmel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Somatex; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: PFM Medical; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sonoscape ; Leadership role, Shareholder/Stockholder/Stock options, partial non-profit ownership : WSG (Westdeutsche Studiengruppe); Leadership role: AGO (Arbeitsgemeinschaft Gynäkologische Onkologie); Research grant/Funding (institution): Somatex. L.M. Manso Sanchez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astra; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. Y.W. Moon: Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Eisai; Research grant/Funding (self): Dong-A ST; Research grant/Funding (self): Chong Kun Dang; Research grant/Funding (self): Celltrion. R. Villanueva Vazquez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Eisai. R. Wuerstlein: Advisory/Consultancy: Agendia; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Carl Zeiss; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: GSK; Advisory/Consultancy: Hexal; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Mundipharma; Advisory/Consultancy: Nanostring; Advisory/Consultancy: Novartis; Advisory/Consultancy: Odonate; Advisory/Consultancy: Paxman; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Puma Biotech; Advisory/Consultancy: Riemser; Advisory/Consultancy: Roche; Advisory/Consultancy: Sandoz; Advisory/Consultancy, Research grant/Funding (self): Seattle Genetics; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self): Palleos; Full/Part-time employment: Klinikum der Univ München; Advisory/Consultancy: Tesaro Bio; Advisory/Consultancy: Teva. Y. Wang: Honoraria (self): Yinghui Want; Honoraria (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. H. Han: Speaker Bureau/Expert testimony: Lilly ; Research grant/Funding (institution): Department of Defense; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Daiichi Pharma; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Horizon; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Maker Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Prescient; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Zymeworks . All other authors have declared no conflicts of interest.