Open-label, phase II study of ladiratuzumab vedotin (LV) for unresectable locally advanced or metastatic solid tumors

초록

Background LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel, investigational, intravenous, humanized immunoglobulin G1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E, which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase I study, LV (2.5 mg/kg every 21 days) was well tolerated and demonstrated encouraging efficacy in previously treated patients with metastatic breast cancer (Modi 2017). Since more frequent, fractionated dosing is associated with improved efficacy and/or safety of other ADCs (Beeram 2012), this study is currently evaluating the safety and efficacy of weekly LV (Q1W) dosing (Days 1, 8, and 15 of every 3-week cycle) in patients with advanced solid tumors with various LIV-1 expression (small cell lung cancer, non-small cell lung cancer [squamous and nonsquamous], head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, advanced gastric and gastroesophageal junction adenocarcinoma, metastatic castration-resistant prostate cancer [mCRPC], and melanoma). Trial design SGNLVA-005 (NCT04032704) is an ongoing, 2-part, open-label, phase II study evaluating LV monotherapy in patients with 8 different advanced solid tumors: Part A (LV 2.5 mg/kg every 3 weeks; n = up to 72) and Part B (LV 1.0 or 1.25 mg/kg Q1W; n = up to 252 total). Parts A and B (LV 1.0 mg/kg) are closed. Part B (LV 1.25 mg/kg Q1W) is currently enrolling previously treated patients with unresectable locally advanced or metastatic disease (n = ∼30 per cohort). All cohorts except mCRPC require patients to have measurable disease per response evaluation criteria in solid tumors (RECIST v1.1). All patients must have an Eastern Cooperative Oncology Group score of ≤1 and adequate organ function. Primary study objectives are objective tumor response rates for all cohorts plus prostate-specific antigen response rate for the mCRPC cohort. Key secondary objectives include safety, progression free survival, and overall survival. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial identification SGNLVA-005. Editorial acknowledgement Joseph Giaconia (MMS Holdings). Legal entity responsible for the study Seagen Inc. Funding Seagen Inc. Disclosure H. Arkenau: Financial Interests, Institutional, Full or part-time Employment: HCA Healthcare UK; Non-Financial Interests, Institutional, Advisory Board: Bicycle; Non-Financial Interests, Personal, Advisory Board: IOnctura; Financial Interests, Personal, Advisory Board: Servier; Non-Financial Interests, Institutional, Advisory Board: Beigene; Financial Interests, Personal, Speaker’s Bureau: Guardant. T. Mekhail: Other, Personal, Invited Speaker: Takeda. D. Cortinovis: Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Non-Financial Interests, Personal, Principal Investigator: Seagen. N. Gabrail: Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: Chemiocare; Financial Interests, Funding: Amgen; Financial Interests, Funding: Bayer; Financial Interests, Funding: Chemiocare; Financial Interests, Funding: Kartos Therapeutics; Financial Interests, Funding: Seagen; Financial Interests, Speaker’s Bureau: Janssen Oncology; Financial Interests, Speaker’s Bureau: Karyopharm Therapeutics; Financial Interests, Speaker’s Bureau: Taiho Pharma; Financial Interests, Speaker’s Bureau: Tesaro/DGSK; Financial Interests, Other, Travel expenses: Oncology Suppl