A Phase 1 study of the anti-tissue factor antibody-drug conjugate XB002 in patients with advanced solid tumors (JEWEL-101): initial results from the dose-escalation stage

Background: XB002 is an antibody-drug conjugate (ADC) composed of a high-affinity tissue factor (TF)-directed human monoclonal antibody conjugated to novel cytotoxic payload, ZymeLink Auristatin. TF, transmembrane protein, functions as FVIIa receptor, initiating the extrinsic coagulation cascade. TF also expressed in multiple tumor types. demonstrated antitumor activity pre-clinical studies across types and did not perturb coagulation. Presented here are initial results from dose-escalation stage JEWEL-101 study with advanced solid tumors. Materials methods: This phase 1, open-label, multicenter, first-in-human trial (NCT04925284) consists tumor-specific cohort-expansion stages. Pts ≥18 years tumors limited treatment options being enrolled. must have ECOG PS 0–1 adequate organ function. In stage, cohorts 3– 12 pts enrolled using interval 3 + design. The primary objective for this determine maximum tolerated dose (MTD) recommended (RD) XB002. Results: At cutoff on 13 May 2022, 15 were four levels (XB002 IV Q3W): 0.16 mg/kg (n = 3); 0.5 1.0 6); 1.5 3). Median age was 63 (range 45–79); 67% had 1. prior lines non-radiation anticancer therapy 2–8). No dose-limiting toxicity observed; MTD/RD has yet been determined. most common reason discontinuation radiographic progression 8). All treatment-emergent adverse event (TEAE), but no grade 4 or 5 TEAEs seen. (33%) unrelated bleeding events peripheral neuropathy observed. treatment-related AEs (TRAEs) £2 resolved next dose: these included ocular toxicities 2, 1 dry eyes 2 conjunctivitis same pt at mg/kg), fatigue nausea each, all 1), chills, edema, skin infection, vomiting 1). Two serious occurred (COVID-19 pneumonia diarrhea). Pharmacokinetic (PK) analysis showed that Cmax AUC increased increasing dose. Total intact ADC PK similar, suggesting stable vivo. Free payload over 300-fold lower than doses (<0.5 ng/mL). Conclusions: Q3W well manageable TRAEs, including toxicities, neuropathy. revealed appropriate exposure very low free payload. Dose-escalation ongoing updated data will be presented. Conflict interest: Ownership: Shailaja Uttamsingh, Jing Li, Mustafa Syed: Exelixis. Anthony Tolcher: Pyxis (Inst). Advisory Board: Susanna Ulahannan: Array BioPharma Bayer Eisai Incyte Syros Pharmaceuticals Research Funding - Abbvie (Inst) Adlai Nortye ArQule Astex AstraZeneca atreca Boehringer Ingelheim Bristol-Myers Squibb Celgene CicloMed Erasca, Inc evelo biosciences Exelixis G1 Therapeutics GlaxoSmithKline IgM Biosciences Klus Pharma Macrogenics Merck Mersana OncoMed Pfizer Regeneron Revolution Medicines Synermore biologics Takeda Tarveda Tempest Tesaro Vigeo Melissa Johnson: Amgen Astellas Axelia Oncology Black Diamond Calithera CytomX Daiichi Sankyo EcoR1 Capital Editas Medicine EMD Serono Genentech/Roche Genmab Gritstone Bio IDEAYA ITeos Janssen Lilly Mirati Oncorus Ribon Sanofi Turning Point WindMIL AbbVie Aclaris Adagene Agenus Aro Biotherapeutics Asana Ascentage Aximmune BioInvent BluPrint Sankyo, Inc. Deka Eleven Elucida Gilde Healthcare HBM Partners HiberCell IDEA Ikena Immuneering Immunome Immunomet IMPACT Jazz Karma Lengo Mekanistic Menarini Nanobiotix NBE Ocellaris Partner Pelican Pieris Pierre Fabre Ryvu Seattle Genetics Senti SK Life Sciences Sotio Spirea Sunshine Guojian Transcenta Transgene Trillium Vincerx Zentalis ZielBio Zymeworks Corporate-sponsored Research: Acerta Adaptimmune Apexigen Arcus Artios Atreca BeiGene BerGenBio BioAtla Carisma Checkpoint Corvus Curis Dracen Dynavax Technologies Elicio Fate Genocea Guardant Health Harpoon Helsinn Hengrui Pharmaceutical Hutchison MediPharma IGM Immunocore Impact Jounce Kadmon Kartos Loxo Lycera Memorial Sloan-Kettering Cancer Center Merus NeoImmuneTech Neovia Novartis Numab Nuvalent, Palleon PMV Rain RasCal Relay Rubius Seven Eight Biopharmaceuticals Shattuck Labs Silicon Stem CentRx Syndax TCR2 Tizona Therapeutics, Tmunity University Michigan Vyriad Y-mAbs Haeseong Park: Ambrx Aprea BJ Bioscience Five Prime Genentech Gilead Gossamer ImmuneOncia Immunomedics MabSpace MedImmune Medivation Millennium Oncologie PsiOxus Puma Biotechnology Roche Biologics Taiho TopAlliance Vedanta Vertex Xencor Andrae Vandross: Mabwell (Shanghai) Astra Zeneca Aminex BioOneCure Elpiscience Biopharma Nanjing Immunophage Biotech Chugai Lyvgen NGMBio Zhuhai Yufan Biotechnologies siRNAomics Sorrento therapeutics Xilio ABL Amphivena Apros Arcellx ARMO BioSciences Arrys Basilea Bioinvent Birdie Boston Biomedical CStone Deciphera eFFECTOR Inhibrx Innate & Development K-Group Beta Kechow Kiromic Sharp Dohme Naturewise NextCure Nitto Odonate ORIC Qilu Puget Sound Samumed Shanghai HaiHe Spring Bank Symphogen Synthorx Other Substantive Relationships: Travel, Accommodations, Expenses Sanofi. Biosciences. Employment Next Oncology. Leadership Expert Testimony – Immunogen. Employment: