Abstract 1033TiP
Background
In early clinical studies, agonistic antibodies targeting the T-cell costimulatory receptors OX40 and CD137 have shown immune-stimulatory effects. Dose-limiting hepatotoxicity significantly hindered further development of CD137 monotherapies. FS120 is a novel tetravalent bispecific antibody incorporating OX40 binding into the Fc-region (termed an Fcab) and CD137 Fabs in a natural human IgG1 antibody and with silenced FcyR activity for reduced toxicity, as shown in preclinical safety studies. FS120 crosslinks and clusters the receptors eliciting a robust immune stimulation and activity in mouse tumor models, independent of FcyR crosslinking (Gaspar et al 2020, Cancer Immunology Research doi: 10.1158/2326-6066). FS120 has the potential to deliver tumor-agnostic clinical efficacy with good tolerability.
Trial design
This FiH study is an open-label dose escalation and cohort expansion study in subjects with advanced malignancies (NCT04648202). FS120 monotherapy is administered once every 4 weeks IV in 28-day treatment cycles until progression, unacceptable toxicity, withdrawal, or death. Primary objectives are to determine safety and tolerability and the RP2D. Secondary objectives include determining PK profiles, preliminary evidence of efficacy, immunogenicity, and pharmacodynamic (PD) profile. Subjects will be enrolled with a maximum of three prior systemic regimens including no more than one prior line of an immune-checkpoint blockade containing regimen. The study has an accelerated dose titration (ADT) involving single-subject cohorts followed by classical 3+3 design and dose expansion cohorts to further characterise safety, PK/PD and clinical efficacy. Subjects are monitored for safety, tolerability, efficacy and other endpoints. Translational studies assess immune cell proliferation and activation in the periphery, soluble peripheral PD biomarker levels and the correlation of FS120 exposure with selected PD markers of target engagement and response. Exploratory translational endpoints will also be included in the study. Study enrolment began December 2020.
Clinical trial identification
NCT04648202.
Editorial acknowledgement
Legal entity responsible for the study
F-star Beta Ltd.
Funding
F-star Therapeutics.
Disclosure
K. Papadopoulos: Financial Interests, Personal, Advisory Role: Basilia; Financial Interests, Personal, Advisory Role: Turning Point Therapeutics; Financial Interests, Personal, Advisory Role: Bicycle Therapeutics; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: MedImmune; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Regeneron; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Calithera Biosciences; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Peloton Therapeutics; Financial Interests, Institutional, Funding: ADC Therapeutics; Financial Interests, Institutional, Funding: 3D Medicines; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Mersana; Financial Interests, Institutional, Funding: MabSpace Biosciences; Financial Interests, Institutional, Funding: Jounce Therapeutics; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: AnHeart; Financial Interests, Institutional, Funding: F-star Therapeutics; Financial Interests, Institutional, Funding: Linneaus; Financial Interests, Institutional, Funding: Mirati; Financial Interests, Institutional, Funding: Tempest Therapeutics; Financial Interests, Institutional, Funding: Treadwell Therapeutics; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Syros Pharmaceuticals. T.A. Yap: Financial Interests, Institutional, Funding: Artios; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Clovis; Financial Interests, Institutional, Funding: Constellation; Financial Interests, Institutional, Funding: Cyteir; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Forbius; Financial Interests, Institutional, Funding: F-star Therapeutics; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: ImmuneSensor; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Jounce; Financial Interests, Institutional, Funding: Karyopharma; Financial Interests, Institutional, Funding: Kyowa; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Ribon Therapeutics; Financial Interests, Institutional, Funding: Regeneron; Financial Interests, Institutional, Funding: Repare; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Scholar Rock; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Institutional, Funding: Vertex Pharmaceuticals; Financial Interests, Personal, Advisory Role: Almac; Financial Interests, Personal, Advisory Role: Aduro; Financial Interests, Personal, Advisory Role: Atrin; Financial Interests, Personal, Advisory Role: Axiom; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Calithera; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: Cybrexa; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: F-star Therapeutics; Financial Interests, Personal, Advisory Role: Guidepoint; Financial Interests, Personal, Advisory Role: Ignyta; Financial Interests, Personal, Advisory Role: I-Mab; Financial Interests, Personal, Advisory Role: Jansen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Repare; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Rubius; Financial Interests, Personal, Advisory Role: Schrodinger; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Varian; Financial Interests, Personal, Advisory Role: Zai Labs; Financial Interests, Personal, Advisory Role: AstraZeneca. S.A. Piha-Paul: Financial Interests, Institutional, Funding: Abbvie Inc; Financial Interests, Institutional, Funding: ABM Therapeutics Inc; Financial Interests, Institutional, Funding: Acepodia Inc; Financial Interests, Institutional, Funding: Alkermes; Financial Interests, Institutional, Funding: Aminex Therapeutics; Financial Interests, Institutional, Funding: Amphivena Therapeutics Inc; Financial Interests, Institutional, Funding: BioMarin Pharmaceutical Inc; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Cerulean Pharma Inc; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co, Ltd; Financial Interests, Institutional, Funding: Curis Inc; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: ENB Therapeutics; Financial Interests, Institutional, Funding: Five Prime Therapeutics; Financial Interests, Institutional, Funding: F-star Therapeutics; Financial Interests, Institutional, Funding: Gene Quantum; Financial Interests, Institutional, Funding: Genmab A/S; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Helix BioPharma Corp; Financial Interests, Institutional, Funding: Incyte Corp; Financial Interests, Institutional, Funding: Jacobio Pharmaceuticals Co. Ltd; Financial Interests, Institutional, Funding: MedImmune LLC; Financial Interests, Institutional, Funding: Medivation Inc; Financial Interests, Institutional, Funding: Merck Sharp and Dohne Corp; Financial Interests, Institutional, Funding: Novartis Pharmaceuticals; Financial Interests, Institutional, Funding: Pieris Pharmaceuticals Inc; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Principa Biopharma Inc; Financial Interests, Institutional, Funding: Puma Biotechnology Inc; Financial Interests, Institutional, Funding: Rapt Therapeutics Inc; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: Silverback Therapeutics; Financial Interests, Institutional, Funding: Taiho Oncology; Financial Interests, Institutional, Funding: Tesaro Inc; Financial Interests, Institutional, Funding: Transthera Bio; Financial Interests, Institutional, Research Grant, P30CA016672 - Core Grant (CCSG Shared Resources): NCI/NIH; Financial Interests, Personal, Advisory Role: Transthera. P. Lorusso: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Other, Data Safety Monitoring Board: Agios; Financial Interests, Personal, Other, Data Safety Monitoring Board: Five Prime; Financial Interests, Personal, Advisory Board: GenMab; Financial Interests, Personal, Other, Data Safety Monitoring Board: Halozyme; Financial Interests, Personal, Other, imCORE Alliance: Roche-Genentech; Financial Interests, Personal, Advisory Role: CytomX; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Role, Consultant: SOTIO; Financial Interests, Personal, Advisory Board: Cybrexa; Financial Interests, Personal, Advisory Board: Agenus; Financial Interests, Personal, Other, Data Safety Monitoring Board: Tyme; Financial Interests, Personal, Advisory Board: IQVIA; Financial Interests, Personal, Advisory Board: TRIGR; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: ImmunoMet; Financial Interests, Personal, Advisory Board: Black Diamond; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: QED Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Shattuck; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Salarius; Financial Interests, Personal, Advisory Board: Silverback; Financial Interests, Personal, Advisory Board: MacroGenics; Financial Interests, Personal, Advisory Board: Kyowa Kirin Pharmaceutical Development; Financial Interests, Personal, Advisory Board: Kineta Inc; Financial Interests, Personal, Advisory Board: Zentalis Pharmaceuticals; Financial Interests, Personal, Advisory Board: Molecular Templates; Financial Interests, Personal, Advisory Board: ABL Bio; Financial Interests, Personal, Advisory Role, Consultant: SK Life Science; Financial Interests, Personal, Advisory Board: STCube Pharmaceuticals; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board, Consultant: I-Mab. S. Hu-Lieskovan: Financial Interests, Personal, Advisory Role, Consultant: Amgen; Financial Interests, Personal, Advisory Role, Consultant: Genmab; Financial Interests, Personal, Advisory Role, Consultant: Xencor; Financial Interests, Personal, Advisory Role, Consultant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consultant: Regeneron; Financial Interests, Personal, Advisory Role, Consultant: Astellas; Financial Interests, Personal, Advisory Role, Consultant: Merck; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Plexxikon; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Neon Therapeutics; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: F-star Therapeutics; Financial Interests, Institutional, Funding: Xencor; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Vedanta; Financial Interests, Institutional, Funding: Kite Pharma; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Checkmate. C.J. Shepherd: Financial Interests, Personal, Full or part-time Employment: F-star Therapeutics; Financial Interests, Personal, Stocks/Shares: F-star Therapeutics. S. Marshall: Financial Interests, Personal, Full or part-time Employment: F-star Therapeutics; Financial Interests, Personal, Stocks/Shares: F-star Therapeutics. J. Holz: Financial Interests, Personal, Advisory Role, Clinical Consultant: F-star Therapeutics. E. Poon: Financial Interests, Personal, Stocks/Shares: F-star Therapeutics. U.B. Grabowska: Financial Interests, Personal, Full or part-time Employment: F-star Therapeutics; Financial Interests, Personal, Stocks/Shares: F-star Therapeutics. L. Kayitalire: Financial Interests, Personal, Full or part-time Employment: F-star Therapeutics; Financial Interests, Personal, Stocks/Shares: F-star Therapeutics.