Abstract 555TiP
Background
The integrins comprise a multifaceted family of membrane-associated proteins that regulate cellular adhesion, motility and cytokinesis. Higher levels of integrin beta-6 predict poorer outcomes in patients with solid tumors such as colorectal, non-small cell lung, gastric and cervical cancers. The vedotin SGN-B6A is an investigational antibody–drug conjugate designed to deliver the cytotoxic agent monomethyl auristatin E (MMAE) to integrin beta-6-expressing cells. Once internalized, intracellular MMAE disrupts microtubules causing cell cycle arrest and apoptosis. Several xenograft models have demonstrated SGN-B6A-mediated tumor growth delay and regression in tumor volume.
Trial design
SGNB6A-001 (NCT04389632) is a phase 1, first-in-human, open-label, multicenter study assessing the safety, tolerability, pharmacokinetics and anti-tumor activity of SGN-B6A in adults with histologically or cytologically confirmed metastatic or unresectable advanced solid tumors. Primary study objectives include evaluation of safety and tolerability of SGN-B6A, identification of the maximum tolerated dose (MTD) and selection of a recommended dosage. Part A enrolls dose-escalation cohorts in which SGN-B6A will initially be given IV to patients on Days 1, 8 and 15 of 21-day cycles. The mTPI design is used to guide dose escalation and identify the MTD with a target dose-limiting toxicity rate of 25% and a 5% margin. Part B will have up to 6 disease-specific dose cohorts and a biology cohort. Pre- and post-treatment tumor samples will be collected from the biology cohort to further characterize SGN-B6A activity. The Part B dosage will be based on findings from Part A. Preliminary anti-tumor activity of SGN-B6A will be assessed using RECIST v1.1. Patients must be ≥18 years old with an ECOG performance status 0–1, and standard therapy must have been unsuccessful, intolerable or deemed inappropriate. Patients must have pancreatic adenocarcinoma, non-small cell lung, head and neck squamous cell or cutaneous squamous cell cancer, or breast, esophageal, ovarian, bladder, cervical or gastric cancer. This study is active at sites across the US and Europe.
Clinical trial identification
NCT04389632.
Editorial acknowledgement
Medical writing support was provided by Elliot Piper-Brown, PhD, and editorial support by Travis Taylor, BA, all of Scion, London, supported by Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Alkermes, Amunix, Anaveon, Amcure, AstraZeneca, BMS, Janssen, MSD, Nanobiotix, Nouscom, Novartis, OncoDNA, PharmaMar, Roche/Genentech, Servier, TargImmune, T-knife; Financial Interests, Institutional, Research Grant: Achilles, BeiGene; Financial Interests, Personal, Other, Scientific Board: Adcendo, Chugai Pharmaceuticals, PsiOxus Therapeutics; Financial Interests, Personal and Institutional, Full or part-time Employment: HM Hospitals Group and START Program of Early Phase Clinical Drug Development in Oncology. Medical Oncologist, Clinical Investigator; Director, Clinical Research; Financial Interests, Personal, Other, Ownership: START corporation; Oncoart Associated; International Cancer Consultants; Financial Interests, Personal, Other, Non-for-profit: founder and president 0034 620 423 957: INTHEOS (Investigational Therapeutics in Oncological Sciences. A. Hollebecque: Financial Interests, Personal, Other, Personal fees: Amgen, BMS, EISAI, Incyte, Debiopharm QED Therapeutics; Non-Financial Interests, Other, Non-financial support: Lilly, Incyte; Financial Interests, Other, Other: AstraZeneca, Roche, Servier. A. Dowlati: Financial Interests, Personal, Other, Consultancy: AbbVie/Stemcentrx, AstraZeneca, Bayer, Bristol-Myers Squibb, G1 Therapeutics, Ipsen, Seagen, Takeda, Merck; Financial Interests, Institutional, Other, Research Funding/Grants: AbbVie/Stemcentrx, Amgen, Bayer, Bristol-Myers Squibb, EMD Serono, Ipsen, Lilly/ImClone, Mirati Therapeutics, Regeneron, Seagen, Symphogen, Takeda, Tesaro, United Therapeutics, Harpoon Therapeutics. S.A. Piha-Paul: Financial Interests, Institutional, Other, Research support: AbbVie, Inc.; ABM Therapeutics, Inc.; Acepodia, Inc; Alkermes; Aminex Therapeutics; Amphivena Therapeutics, Inc.; BioMarin Pharmaceutical, Inc; Boehringer Ingelheim; Bristol Myers Squib; Cerulean Pharma, Inc.; Chugai Pharmaceutical Co., Ltd; Curis, Inc.; Financial Interests, Personal, Other, Consultancy: TransThera Bio. V. Galvao: Financial Interests, Personal, Other, Travel expenses: F Hoffmann-La Roche Ltd. J. Lopez: Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Institutional, Other, Research Funding/Grants: Roche-Genentech, Genmab, Basilea. B. Bockorny: Financial Interests, Institutional, Other, Research support: NanoView Biosciences; Financial Interests, Personal, Other, Travel Expenses: Erytech Pharma. F. Braiteh: Financial Interests, Personal, Other, Advisory Board/Honorarium: Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Clovis, Eisai, Eli Lilly, Exelixis, Gilead, Incyte, Ipsen, Lexicon, Loxo Oncology, Merck, Pfizer, Roche/Genentech, Taiho, Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Clovis, Eli Lilly, Exelixis, Incyte, Ipsen, Loxo Oncology, Merck, Roche/Genentech, Taiho, Takeda; Financial Interests, Personal, Other, Travel Expenses: Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Exelixis, Incyte, Ipsen, Loxo Oncology, Merck, Roche/Genentech. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. R.E. Sanborn: Financial Interests, Personal, Other, Consultancy: AstraZeneca, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Genentech/Roche, Janssen Oncology, Lilly, Macrogenics; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca; Financial Interests, Institutional, Other, Research Funding/Grants: AstraZeneca, Bristol-Myers Squibb, MedImmune, Merck; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca. P. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Invited Speaker, Travel Expenses: Seagen Inc.; Financial Interests, Personal and Institutional, Other, Stock Ownership: Seagen Inc.. N. Nazarenko: Financial Interests, Personal and Institutional, Full or part-time Employment: Seagen, Ipsen; Financial Interests, Personal and Institutional, Other, Stock Ownership: Seagen Inc.. A. Patnaik: Financial Interests, Personal, Other, Consultancy: Bayer Bristol-Myers Squibb, Genentech/Roche, Merck, Novartis, Seagen, Silverback Therapeutics; Financial Interests, Personal, Other, Honoraria: Texas Society of Clinical Oncology; Financial Interests, Institutional, Other, Research Funding/Grants: AbbVie, Arcus Ventures, Astellas, Bolt, Corvus, Daiichi Sankyo, Exelixis, Five Prime, Fochon Pharma, Forty Seven, Infinity Pharma, Ionova, Klus Pharma, Lilly, Livzon, Merck, Pieris Pharma, Plexxikon, Pfizer, Sanofi, Seagen, Surface Oncology, Symphogen, Sy. All other authors have declared no conflicts of interest.