Abstract 556TiP
Background
STn is a tumor-associated carbohydrate antigen with high prevalence across various solid tumor types, including ovarian and non-small cell lung cancer (NSCLC). While its expression is restricted in normal tissues, it presents with several tumor-associated proteins, such as MUC1 and MUC16. STn is thought to influence cancer progression by affecting cell adhesion, migration and propagation of invasiveness, and has been linked to advanced disease, chemotherapy resistance, and decreased survival. SGN-STNV is an investigational antibody–drug conjugate which directs monomethyl auristatin E (MMAE) to STn-expressing cells. In preclinical studies, SGN-STNV showed promising inhibition of metastatic growth and improved animal survival in STn-expressing tumor models.
Trial design
SGNSTNV-001 (NCT04665921) is a phase 1, open-label, multicenter, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-STNV in adults with select advanced solid tumors. Part A (dose escalation) and Part B (dose expansion) will include up to 25 and 180 patients (in up to 6 expansion cohorts), respectively. The primary endpoint is to evaluate safety and tolerability, and identify the maximum tolerated dose, recommended dose, and dosing schedule for SGN-STNV. Secondary endpoints include antitumor activity, PK and immunogenicity of SGN-STNV. In addition, biomarkers relating to response, toxicity, PK/pharmacodynamics, and resistance to SGN-STNV will be assessed. Eligible patients must be 18 years or older with advanced/refractory solid tumors in any of the following cancers: NSCLC, HER2-negative breast cancer, ovarian, cervical, endometrial, esophageal, gastric, gastroesophageal junction or colorectal cancer, appendiceal or exocrine pancreatic adenocarcinoma, or pseudomyxoma peritonei of unknown origin. Patients must have an Eastern Cooperative Oncology Group performance status score of 0 or 1 and measurable disease per RECIST version 1.1. Study accrual is ongoing in the USA, Canada, and Europe.
Clinical trial identification
NCT04665921.
Editorial acknowledgement
Medical writing support was provided by Calum Suggett, MSc, 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
N.J. Lakhani: Financial Interests, Personal, Other, Consultancy: Innovent Biologics; Financial Interests, Institutional, Other, Research Funding/Grants: Alexion, Alexo, Alpine Bio, Alpine Immune Sciences, Apexian, Asana, Ascentage, Astellas, BeiGene, Biologics, Celgene, Cerulean, Constellation, Coordination Therapeutics, CytomX, Epizyme, Formation, Forty-Seven, Genmab, Helsinn, Ikena, Incyte, InhibTx, Inn. I. Braña: Financial Interests, Personal, Other, Consultancy: Achilles Therapeutics, Cancer Expert Now, eTheRNA Immunotherapies, Merck Sharp & Dohme, Rakuten Medical, Sanofi; Financial Interests, Other, Research Funding/Grants: AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, Janssen, Kuro Oncology, Merck Sharp & Dohme, Nanobiotix, Novartis, Orion Pharma, Pfizer, Roche, Seagen, Shattuck Labs; Financial Interests, Speaker’s Bureau: Bristol-Myers Squibb, Merck Serono, Roche; Financial Interests, Other, Travel Expenses: AstraZeneca Spain, Merck Serono. V.K. Chiu: Financial Interests, Personal, Other, Research Funding/Grants: Alkermes, Arcus Biosciences, Incyte, Intra-IMMUSG Pte, Leap Therapeutics, Seagen/Astellas. 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.M. McGoldrick: Financial Interests, Personal and Institutional, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Other, Consultancy: AbbVie and Near Future Allergan; Financial Interests, Personal, Other, Travel, accommodation and expenses: Seagen Inc.; Financial Interests, Personal and Institutional, Other, Stock and other ownership interests: Seagen Inc.; Financial Interests, Institutional, Other, Research Funding/Grants: AbbVie, Janssen and Takeda. A. Minchom: Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Other, Honoraria: Bayer, Chugai Pharma, Faron Pharma, Merck, Novartis; Financial Interests, Institutional, Other, Research Funding/Grants: Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: Amgen. X. Tian: Financial Interests, Personal and Institutional, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal and Institutional, Other, Stock and other ownership interests: 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 (TxSCO); Financial Interests, Institutional, Other, Research Funding/Grants: AbbVie, Arcus Ventures, Astellas Pharma, Bolt Biotherapeutics, Corvus, Daiichi Sankyo, Exelixis, Five Prime Therapeutics, Fochon Pharmaceuticals, Forty Seven, Infinity Pharmaceuticals, Ionova, Klus Pharma, Lilly, Livzon, Merck, Pfizer, Pieris Pharmaceutic. All other authors have declared no conflicts of interest.