Abstract 930TiP
Background
Tisotumab vedotin (TV) is an investigational antibody-drug conjugate directed to Tissue Factor (TF). In the phase I/II innovaTV 201 and phase II innovaTV 204 studies, TV demonstrated encouraging antitumor activity with a manageable safety profile in patients (pts) with multiple TF-expressing tumor types. The innovaTV 207 trial is a global, open label, multicenter phase II trial assessing the safety, tolerability, and activity of TV in solid tumors known to express TF. This abstract presents the addition of Part C, testing TV in squamous non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Based on pharmacokinetic (PK) and exposure-response analyses data, we will be evaluating an every other week dosing schedule (2Q4W), which is new across the TV program, in addition to administering TV on Days 1, 8, and 15 of a 28-day cycle in Part C.
Trial design
Up to 92 pts will be enrolled in Part C of innovaTV 207. TV will be administered by IV at 1.2 mg/kg on Days 1, 8, and 15 of a 28-day cycle (3Q4W), or at 1.7 mg/kg on Days 1 and 15 of a 28-day cycle (2Q4W) in pts with SCCHN or NSCLC. This part will start with a safety run-in with 6 pts per dosing schedule. Afterwards, a dose expansion phase will enroll 20 SCCHN (10 3Q4W + 10 2Q4W) and 20 NSCLC (10 3Q4W + 10 2Q4W) pts with the possibility of adding 20 more patients per indication at 1 given dosing schedule to evaluate preliminary antitumor activity. Pts must have measurable disease progression per RECIST v1.1 despite standard of care in locally advanced or metastatic settings (up to 3 prior lines for SCCHN, 2 for squamous NSCLC [3 for pts eligible for a tyrosine kinase inhibitor who should have received such therapy]), and an ECOG score of 0 or 1. The primary endpoint is Investigator-determined (Inv) confirmed objective response rate (ORR) per RECIST v1.1. Secondary endpoints include Inv, duration of response, progression-free survival, overall survival, disease control rate, and time to response, as well as safety and PK parameters. The trial opened in June 2018 and was amended to add Part C in February 2021. The study is enrolling for Part C across 28 sites in 7 countries: US, Canada, Italy, France, UK, Germany, and Spain. Enrollment updates will be provided at the meeting.
Clinical trial identification
NCT03485209; EudraCT 2017-005076-26.
Editorial acknowledgement
MMS Holdings.
Legal entity responsible for the study
Genmab A/S and Seagen Inc.
Funding
Genmab A/S and Seagen Inc.
Disclosure
D. Hong: Financial Interests, Personal and Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Adaptimmune; Financial Interests, Personal and Institutional, Research Grant: Adlai Nortye; Financial Interests, Personal and Institutional, Research Grant, Travel; Consultancy: Amgen; Financial Interests, Personal and Institutional, Research Grant, Travel: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, Travel; Consultancy: Bayer; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal and Institutional, Research Grant, Travel Expenses: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Erasca; Financial Interests, Personal and Institutional, Research Grant: Fate Therapeutics; Financial Interests, Personal and Institutional, Research Grant, Travel; Consultancy: Genentech; Financial Interests, Personal and Institutional, Research Grant, Travel: GlaxoSmithKline; Financial Interests, Personal and Institutional, Research Grant: Ignyta; Financial Interests, Personal and Institutional, Research Grant: Kite; Financial Interests, Personal and Institutional, Research Grant: Kyowa; Financial Interests, Personal and Institutional, Research Grant, Travel: LOXO; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: MedImmune; Financial Interests, Personal and Institutional, Research Grant: Millenium; Financial Interests, Personal and Institutional, Research Grant: Mirati; Financial Interests, Personal and Institutional, Research Grant, Travel: miRNA; Financial Interests, Personal and Institutional, Research Grant: Molecular Templates; Financial Interests, Personal and Institutional, Research Grant: Mologen; Financial Interests, Personal and Institutional, Research Grant: Navier; Financial Interests, Personal and Institutional, Research Grant: NCI-CTEP; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Numab; Financial Interests, Personal and Institutional, Research Grant, Travel; Consultancy: Pfizer; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Seagen; Financial Interests, Personal and Institutional, Research Grant, Travel; Consultancy: Takeda; Financial Interests, Personal and Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Personal and Institutional, Research Grant: Verstatem; Financial Interests, Personal and Institutional, Research Grant: VM Oncology; Financial Interests, Personal, Other, Travel: AACR; Financial Interests, Personal, Other, Travel: ASCO; Financial Interests, Personal, Other, Travel: Celgene; Financial Interests, Personal, Other, Travel: Genmab; Financial Interests, Personal, Other, Travel; Consultancy: Janssen; Financial Interests, Personal, Other, Travel: Philips; Financial Interests, Personal, Other, Travel: SITC; Financial Interests, Personal, Other, Consultancy: Alpha Insights; Financial Interests, Personal, Other, Consultancy: Acuta; Financial Interests, Personal, Other, Consultancy: Axiom; Financial Interests, Personal, Other, Consultancy: Baxter; Financial Interests, Personal, Other, Consultancy: Boxer Capital; Financial Interests, Personal, Other, Consultancy: COG; Financial Interests, Personal, Other, Consultancy: Ecor1; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Personal, Other, Consultancy: Group H; Financial Interests, Personal, Other, Consultancy: Guidepoint; Financial Interests, Personal, Other, Consultancy: HCW Precision; Financial Interests, Personal, Other, Consultancy: Infinity; Financial Interests, Personal, Other, Consultancy: Merrimack; Financial Interests, Personal, Other, Consultancy: Medscape; Financial Interests, Personal, Other, Consultancy: Prime Oncology; Financial Interests, Personal, Other, Consultancy: ST Cube; Financial Interests, Personal, Other, Consultancy: Tavistock; Financial Interests, Personal, Other, Consultancy: Trieza Therapeutics; Financial Interests, Personal, Other, Consultancy: WebMD; Financial Interests, Personal, Advisory Board: Molecular Match; Financial Interests, Personal, Other, Founder: OncoResponse; Financial Interests, Personal, Advisory Board: Presagia Inc. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Innate; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Seagen. C. Steuer: Financial Interests, Personal, Other, Consultancy: Abbvie; Financial Interests, Personal, Other, Consultancy: ARMO Bioscience; Financial Interests, Personal, Other, Consultancy: BerGenBio; Non-Financial Interests, Personal, Officer, Honoraria: Merck; Financial Interests, Personal and Institutional, Research Grant: Vaccinex. M.H. Taylor: Financial Interests, Personal, Other, Consultancy: Arqule; Financial Interests, Personal, Other, Consultancy: Array Biopharma; Financial Interests, Personal, Other, Consultancy: Bayer; Financial Interests, Personal, Other, Consultancy: Blueprint; Financial Interests, Personal, Other, Consultancy: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultancy: Eisai Inc; Financial Interests, Personal, Other, Consultancy: Loxo Oncology; Financial Interests, Personal, Other, Consultancy: Novartis; Non-Financial Interests, Personal, Other, Honoraria: Arqule; Non-Financial Interests, Personal, Other, Honoraria: Array Biopharma; Non-Financial Interests, Personal, Other, Honoraria: Bayer; Non-Financial Interests, Personal, Other, Honoraria: Blueprint; Non-Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Honoraria: Eisai Inc; Non-Financial Interests, Personal, Other, Honoraria: Loxo Oncology; Non-Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Eisai Inc; Financial Interests, Personal, Speaker’s Bureau: Blueprint Medicines; Financial Interests, Personal, Speaker’s Bureau: Merk. T.J. George: Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Personal, Advisory Role: Tempus. J. Lacy: Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celgene; Financial Interests, Personal, Other, Consultancy: Deciphera; Financial Interests, Personal, Other, Consultancy: Ipsen; Financial Interests, Personal, Other, Consultancy: KeyQuest Health; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal, Other, Consultancy: Navigant Consulting; Financial Interests, Personal, Other, Consultancy: Sirtex Medical; Financial Interests, Personal, Other, Consultancy: Guidepoint; Financial Interests, Personal and Institutional, Other, Travel Expenses: Lilly. F. Beca: Financial Interests, Personal, Other, Employment: Seagen Inc; Financial Interests, Personal, Ownership Interest: Seagen Inc. L.V. Nicacio: Financial Interests, Personal, Other, Employment: Seagen Inc; Financial Interests, Personal, Ownership Interest: Florence Healthcare; Financial Interests, Personal, Other, Honorarium: Seagen Inc; Financial Interests, Personal and Institutional, Other, Travel: Seagen Inc. I. Soumaoro: Financial Interests, Personal, Other, Employment: Genmab; Financial Interests, Personal, Ownership Interest: Genmab; Financial Interests, Personal and Institutional, Other, Travel Expenses: Genmab; Financial Interests, Institutional, Other, Non-remunerated activity: Genmab. M. Cho: Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Incyte; Financial Interests, Personal, Other, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Ipsen; Financial Interests, Personal, Other, Consultancy: Astellas; Financial Interests, Personal, Other, Consultancy: Taiho; Financial Interests, Personal, Other, Consultancy: Exelixis; Financial Interests, Personal, Other, Consultancy: QED; Financial Interests, Personal, Other, Consultancy: I-Mab; Financial Interests, Personal, Other, consultancy: Tempus; Financial Interests, Personal, Other, consultancy: Seagen; Financial Interests, Personal, Other, consultancy: HelioDx; Financial Interests, Personal, Other, Consultancy: Bayer; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Genentech; Non-Financial Interests, Personal, Other, Honoraria: Amgen; Non-Financial Interests, Personal, Other, Honoraria: Incyte; Non-Financial Interests, Personal, Other, Honoraria: Eisai; Non-Financial Interests, Personal, Other, Honoraria: Ipsen; Non-Financial Interests, Personal, Other, Honoraria: Astellas; Non-Financial Interests, Personal, Other, Honoraria: Taiho; Non-Financial Interests, Personal, Other, Honoraria: Exelixis; Non-Financial Interests, Personal, Other, Honoraria: QED; Non-Financial Interests, Personal, Other, Honoraria: I-Mab; Non-Financial Interests, Personal, Other, Honoraria: Tempus; Non-Financial Interests, Personal, Other, Honoraria: Seagen; Non-Financial Interests, Personal, Other, Honoraria: HelioDx; Non-Financial Interests, Personal, Other, Honoraria: Bayer; Non-Financial Interests, Personal, Other, Honoraria: AstraZeneca; Non-Financial Interests, Personal, Other, Honoraria: Genentech; Non-Financial Interests, Personal, Other, Honoraria: Pfizer; Non-Financial Interests, Personal, Other, Honoraria: Natera; Non-Financial Interests, Personal, Other, Honoraria: Taiho; Non-Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Seagen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Natera; Financial Interests, Personal, Speaker’s Bureau: Taiho. All other authors have declared no conflicts of interest.