First-in-human phase I dose escalation study of ALG.APV-527, a 5T4 tumor antigen-conditional 4-1BB bispecific antibody, in patients with advanced solid tumors, demonstrates positive safety, signals of biological activity and patients with lasting stable disease

Background4-1BB-targeted therapies have the potential to address an important need in immuno-oncology, providing clinical benefits in checkpoint inhibitor refractory patients. ALG.APV-527 is a bispecific antibody targeting co-stimulatory receptor 4-1BB and oncofetal antigen 5T4, expressed on multiple solid tumor types. Based on its profile, 5T4 is an attractive tumor-associated antigen for bispecific therapy, enabling targeted delivery of an immune agonist.MethodsThe Phase I study is a first-in-human, open-label, multicenter trial consisting of six cohorts (0.1-15 mg/kg) in a 3+3 dose escalation of ALG.APV-527 monotherapy, administered intravenously Q2W, in adult patients with advanced solid tumors. Eligibility is limited to patients with tumor types identified as likely to express 5T4 antigen. Key endpoints include safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity of ALG.APV-527.ResultsALG.APV-527 has been well tolerated; a total of 14 patients experienced 73 treatment-related adverse events. Most events were mild to moderate and manageable in the clinic; G1=30 (41%), G2=32, (44%), G3=8 (11%), G4=3 (4%), G5=0. One patient experienced a G4 dose limiting toxicity of febrile neutropenia. An MTD has yet to be determined. Exposure has shown to be associated with serum protein changes relevant to ALG.APV-527 activity. Two heavily pretreated breast cancer patients experienced prolonged stable disease of over 7 months and 11 months (escalated to a higher dose level without any added adverse events) and remains on study.ConclusionsALG.APV-527 demonstrates good tolerability, safety, biological activity, and prolonged SD among two heavily pretreated breast cancer patients. Dose escalation is ongoing to identify MTD and recommended Phase 2 dose.Clinical trial identificationNCT05934539.Legal entity responsible for the studyAptevo Therapeutics and Alligator Bioscience.FundingAptevo Therapeutics and Alligator Bioscience.DisclosureT. Marron: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Genentech, G1 Therapeutics, Arcus, Glenmark, Merck, NGMBio, Glenmark, AbbVie, Fate; Financial Interests, Institutional, Coordinating PI: Regeneron, Genentech, Boehringer Ingelheim, Merck. S. Rosen: Financial Interests, Personal, Stocks/Shares, Stocks: Lilly, Pfizer, BMS, Amgen. J. Powderly II: Financial Interests, Personal and Institutional, Member of Board of Directors: BioCytics ; Financial Interests, Personal, Writing Engagement: Aavocyte; Other, Personal, Advisory Role: Boxer Capital; Financial Interests, Personal, Ownership Interest: Carolina Biooncology Institute, Biocytics, Carolina Biooncology Institute, Biocytics; Financial Interests, Personal, Other: Aavocyte; Non-Financial Interests, Personal and Institutional, Local PI: AbbVie, Alkermes, Apollo, Apros, Arcus, Astellas, AstraZeneca, Medimune, Altreca, BioNTech, BJ Biosciences, Bristol Myers Squibb, Calico Life Sciences, Conjupro Biotherapeutics, Corbus, Cullinan, CytoMx, Fate Therapeutics, FBD Biologics, FLX Bio, Genentech/Roche, Glenmark, I-MAB Pharma, Immune Onc, InCyte, Jounce Therapeutics, Macrogenics, McBrace, Merck, Molecular Templates, Multitude, NexCure, Nuvation, Repertoire, Revolution Medicines, Sairopa, Seattle Genetics, Sequenom, Tempest Therapeutics, Top Alliance BioScience, Trethera, Xilio Therapeutics, Zenshine; Non-Financial Interests, Personal and Institutional, Principal Investigator: Adagene; Financial Interests, Personal and Institutional, Local PI: Allarity, Aptevo, Aulos, CUE BioPharma, EMD Serono, Gi Innovation, Harbour BioMed, IconOVir Bio, IGM Biosciences, MedKine, Moderna Tx, Peel Therapeutics, Phanes Therapeutics, Pieris Pharmaceuticals, Qurgen, RiboScience, Simcere, SK Life Sciences; Non-Financial Interests, Institutional, Funding: MT Group; Non-Financial Interests, Personal and Institutional, Funding: Nuvation, Preision for Medicine, Replimmune, Sairopa, Revolution Medicine, SK Life Sciences, Stemcell Technologies, Xilis; Financial Interests, Personal and Institutional, Funding: Pioma, Wugen Funding. N. Khaskhely, L. Bonham, C. Taromino, D. Taylor, J. Kumer: D. Huebner, M. Nelson: Financial Interests, Institutional, Full or part-time Employment: Aptevo Therapeutics; Financial Interests, Institutional, Stocks/Shares: Aptevo Therapeutics. P. Ellmark, S.V. Ambarkhane: Financial Interests, Personal, Full or part-time Employment: Alligator Bioscience; Financial Interests, Personal, Stocks/Shares: Alligator Bioscience. S. Fritzell: Financial Interests, Personal, Full or part-time Employment: Alligator Bioscience AB; Financial Interests, Personal, Stocks/Shares: Alligator Bioscience AB; Non-Financial Interests, Project Lead: Alligator Bioscience AB. A. Alahmadi: Financial Interests, Institutional, Research Grant: NCCN-AstraZeneca; Financial Interests, Institutional, Local PI: Genentech, Glided, Tempus; Non-Financial Interests, Advisory Role: Tempus; Non-Financial Interests, Principal Investigator: Aptevo, Lilly Oncology. All other authors have declared no conflicts of interest.