Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial.

George Nintos, Sophia N Karagiannis, Debra H Josephs, Heather J Bax, Sarah Pinder, Cheryl Gillett, Jitesh Chauhan, Chara Stavraka, Atousa Khiabany, Kristina M Ilieva, Mano Nakamura, Giulia Pellizzari, Hannah J Gould, Gary Doherty, Ionut-Gabriel Funingana, Vineet Kwatra, James Spicer, Chris Selkirk, Simon Carroll, Sarah Mellor, Paul Jones, Claire Barton, Silvana Canevari, Mariangela Figini, Stephen J Till, Christopher J Corrigan, Gareth J Veal, Rowan Miller, Rebecca Kristeleit, Udai Banerji, Ana Montes, Bristi Basu

Journal: Nature communications 2023;14(1):4180

PMID: 37491373

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Abstract

All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 μg-12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer.

Address: School of Cancer and Pharmaceutical Sciences, King's College London, London, UK. [email protected].; Cancer Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK. [email protected].; Cambridge University Hospitals NHS Foundation Trust, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, UK.; Cancer Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.; Institute of Cancer Research and Royal Marsden Hospital NHS Foundation Trust, Sutton, UK.; University College London, London, UK.; Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.; King's Centre for Lung Health, School of Immunology and Microbial Sciences, King's College London, London, UK.; ANP2, Department of Advanced Diagnostics, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.; Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.; Centre for Drug Development, Cancer Research UK, London, UK.; Barton Oncology Ltd, Hertfordshire, UK.; UCB Pharma Ltd., Slough, UK.; Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, London, UK.; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK.; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.; King's Health Partners Cancer Biobank, Guy's and St Thomas' NHS Foundation Trust, London, UK.; Breast Cancer Now Research Unit, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.

DOI: 10.1038/s41467-023-39679-9

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MeSH Terms: Female, Humans, Immunoglobulin E, Antibodies, Monoclonal, Ovarian Neoplasms, Basophils, Folic Acid