87TiP - Phase I expansion study of the tissue factor (TF)–targeting antibody-drug conjugate (ADC) XB002 as a single-agent and combination therapy in patients with advanced solid tumors (JEWEL-101)

Background

XB002 is a novel ADC composed of a high-affinity TF-directed human monoclonal antibody conjugated to zovodotin, an auristatin-based payload with a protease-cleavable linker. High TF expression has been observed in many tumor types, including squamous cell carcinoma of head and neck (SCCHN), non–small cell lung cancer (NSCLC), pancreatic, prostate, cervical, endometrial, and epithelial ovarian cancer (EOC), and is associated with poor prognosis. In preclinical studies, XB002 showed encouraging antitumor activity without interfering with coagulation. JEWEL-101 (NCT04925284) is a multicenter, phase 1 first-in-human trial, designed to determine the recommended dose and/or maximum tolerated dose of XB002 alone or in combination with nivolumab or bevacizumab and evaluate safety and antitumor activity in advanced solid tumors. Presented is the design of the cohort expansion stage.

Trial design

The multi-cohort expansion phase of JEWEL-101 will assess the safety, PK, and efficacy of XB002. Patients (pts) must be aged ≥18 years with inoperable, advanced, metastatic, or recurrent tumors, progression during/following last systemic therapy, ECOG PS 0/1, adequate organ and marrow function, and archival or fresh tumor tissue. Prior treatment with TF-targeting or auristatin-based ADCs is not permitted. Pts with significant ocular disorders are excluded. Concomitant anticoagulants are permitted, and pts with peripheral neuropathy not impacting activities of daily living are allowed. Expansion cohorts for single-agent XB002 include NSCLC, EOC, cervical, SCCHN, pancreatic, esophageal SCC, metastatic castration-resistant prostate cancer, triple-negative breast cancer, hormone receptor-positive breast cancer, endometrial cancer, and a tumor-agnostic TF-expressing cohort. Expansion cohorts for combination therapy include NSCLC, SCCHN, and esophageal SCC (XB002 + nivolumab), and EOC (XB002 + bevacizumab). The primary objective is ORR per RECIST v1.1 by investigator. Secondary objectives include safety, PK, immunogenicity, PFS, DOR, and OS. Enrollment is ongoing in the US, Europe, and Asia-Pacific region.

Clinical trial identification

NCT04925284.

Legal entity responsible for the study

Exelixis, Inc.

Funding

This study is funded by Exelixis, Inc.

Disclosure

S. Ulahannan: Financial Interests, Institutional, Research Funding: AbbVie, Inc, Adlai Nortye, ArQule, Inc, AstraZeneca, Atreca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Ciclomed LLC, Erasca, Evelo Biosciences, Inc., Exelixis, G1 Therapeutics, Inc, GSK GSK, IGM biosciences, Incyte, Isofol, Klus Pharma, Inc., Macrogenics, Merck Co. Inc, Mersana Therapeutics, OncoMed Pharmaceuticals, Inc., Pfizer, Regeneron, Inc., Revolution Medicines, Inc., Synermore Biologics Co, Takeda, Tarveda Therapeutics, Tesaro, Tempest, Vigeo Therapeutics Inc.; Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, IgM biosciences. M.L. Johnson: Financial Interests, Institutional, Research Funding: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics. M.C. Weiss: Financial Interests, Personal, Other, Honoraria: 60 minute telephone survey-topic Management of Soft Tissue Sarcoma-8/23/2022: Research America; Financial Interests, Personal, Advisory Board, SpringWorks Ovarian Dysfunction Advisory Board-3/2/2023: Springworks. A. Vandross: Financial Interests, Personal, Full or part-time Employment: NEXT ONCOLOGY; Financial Interests, Personal and Institutional, Research Funding, PAYMENTS MADE TO COMPANY BY SPONSORS: NEXT ONCOLOGY. S. Vidal-Cardenas: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. M. Syed: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. A.W. Tolcher: Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Leadership Role: NEXT Oncology; Financial Interests, Personal, Leadership Role, On the NEXT Oncology Board: NEXT Oncology; Financial Interests, Personal and Institutional, Advisory Role, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, LLC d/b/a NEXT Oncology of which he is President and Founder.: ABBVIE, Inc, Aclaris Therapeutics, AGENUS, Inc., asana biosciences, Ascentage, Axlmmune, Bayer, Blu Print Oncology, Daiichi Sankyo, Inc., gilde healthcare partners, hbm partners, idea Pharma, Immuneering, Immunomet Therapeutics, Inc., Impact Therapeutics US, Inc., Karma Oncology B.V., Kirilys Therapeutics, Inc., Lengo Therapeutics, Inc., Link Immunotherapeutics, Mekanistic Therapeutics, Menarini Ricerche, Mersana, NANOBIOTIX, Novo Nordisk Inc., NervianoMedical Sciences S.r.I. (NMS), Nurix Therapeutics, Ocellaris Pharma, Inc. & Eli Lilly, Partner Therapeutics, Pfizer Inc., Qualigen Therapeutics, PIERRE FABRE, Roche, RYVU therapeutics, Seattle Genetics, SK Life Science, SOTIO Biotechnology Co., Spirea Limited Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd, Transcenta Therapeutics Inc., Transgene, Trillium Therapeutics Inc., Verastem Oncology, VRISE Therapeutics, Inc., Zentalis Pharmaceuticals; Financial Interests, Personal and Institutional, Expert Testimony, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, LLC d/b/a NEXT Oncology of which he is President and Founder.: Immunogen; Financial Interests, Personal and Institutional, Proprietary Information, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, LLC d/b/a NEXT Oncology of which he is President and Founder.: Ascentage Pharma, Zentalis; Financial Interests, Personal and Institutional, Advisory Board, Fees for consulting and advisory board memberships for Dr. Anthony Tolcher are paid to New Experimental Therapeutics, LLC d/b/a NEXT Oncology of which he is President and Founder.: ADAGENE, Inc., aro biotherapeutics, BIOINVENT, Boehringer Ingelheim International GmbH, Bright Peak Therapeutics, Deka Biosciences, Eleven Bio, ELUCIDA, emd serono/ Merck KGaA, Hiber Cell, Inc., Ikena Oncology, IMMUNOME, Janssen Global Services, LLC, nbe therapeutics, Pelican, JAZZ, Pieris Pharma, PYXIS Oncology, Senti Biosciences, Vincerx, ZielBio, Inc., Zymeworks Biopharmaceuticals Inc., MIRATI, Roche.