2018 ASCO Annual Meeting!
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
CD205-Shuttle study: A first-in-human trial of MEN1309/OBT076 an ADC targeting CD205 in solid tumor and NHL.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #427a)
J Clin Oncol 36, 2018 (suppl; abstr TPS2606)
Author(s): Elena Garralda, Josep Tabernero, Victor Moreno Garcia, Maria José De Miguel, Elizabeth Ruth Plummer, Guy Heinrich Maria Jerusalem, Michele Spina, Christian Rohlff, Abrahim Fandi, Serena Buontempo, Mariagiuseppa Matera, Mario Cioce, D'Angiolella Paola, Monica Binaschi, Giuseppe Merlino, Paolo Mazzei, Cristina Rossi, Giulia Tonini, Cecilia Simonelli, Andrea Ugo Enrico Pellacani; Medical Oncology Department, Vall d’Hebron University Hospital; Molecular Therapeutics Research Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Vall d’Hebron University Hospital, Barcelona, Spain; START Madrid. Fundacion Jimenez Diaz, Madrid, Spain; Centro Integral Oncologico Clara Campal, Madrid, Spain; Northern Centre for Cancer Care, Newcastle-upon-Tyne, United Kingdom; CHU Sart Tilman Liège and Liège University, Liège, Belgium; National Cancer Institute, Aviano, Italy; Oxford Biotherapeutics, Abingdon, United Kingdom; Oxford BioTherapeutics, Abingdon, United Kingdom; MENARINI RICERCHE S.p.A., Firenze, IT; Menarini Ricerche, Firenze, Italy; Menarini Ricerche S.p.A., Firenze, Italy; Menarini Ricerche, Pomezia, Italy
Background: MEN1309/OBT076 is a DM4-loaded Antibody Drug Conjugate (ADC), directed against CD205/Ly75, a type I transmembrane surface protein belonging to the macrophage mannose receptor family. CD205 is therapeutically relevant, because of its broad expression in multiple cancer types, its emerging role at facilitating metastatic invasion and its effective internalization upon antibody binding. Extensive preclinical evidence demonstrated MEN1309 antitumor activity in vitro, in xenograft and patient-derived xenograft (PDX) models. Methods: The CD205-Shuttle study is a two-step, open-label, multicenter, dose-escalation FIH study. Step 1 involves patients affected by different solid tumors, following an Accelerated Titration Design (ATD) whereby 1 patient per dose cohort is enrolled and the dose doubled at each cohort. If grade ≥2 toxicity is observed the trial design is expected to revert to a 3+3 scheme with a Fibonacci ascending dose scheme. Step 2 is designed to test MEN1309/OBT076 at minus 2 levels of the tolerated doses during Step 1 in patients with Non-Hodgkin-Lymphoma (NHL). Each dose level escalation will be subject to the assessment of the Cohort Review Committee (CRC). CD205-positive patients are selected by IHC staining of archived tumor material. Patient with locally advanced or metastatic solid tumor in progression can be included if failed on ≥2 previous cancer treatments and if no standard therapy is available. The primary endpoint is to identify dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MEN1309/OBT076 administered by i.v. infusion once every 21-days. The secondary endpoints includes assessment of pharmacokinetics (PK), immunogenicity, preliminary clinical efficacy of MEN1309/OBT076 and correlation with CD205 expression. Adverse Events (AE) will be graded according to NCI CTCAE v. 4.03. Responses will be evaluated according to RECIST v1.1 and Cheson criteria (2014). Study variables will be presented by dose-cohort and overall using appropriate descriptive statistics. The enrollment began in October 2017 in European sites; up to date 3 cohort levels have been achieved. NCT03403725. NOTE: First and Second author equally contributed to this work Clinical trial information: NCT03403725