1502TiP - A phase I/IIa trial of ChAdOx1 and MVA vaccines against MAGE-A3 and NY-ESO-1

Background

While immunotherapy is a critical modality for the treatment of many cancers, many patients (pts) do not respond to checkpoint blockade. Vaccination against tumour antigens has potential to enhance this, and despite the historically limited success of vaccines in monotherapy, effective immune induction is observed. Prime-boost viral vaccination is a highly potent platform, priming immunity with the CHAdOx1 adenoviral vector, followed by MVA vaccinia vector boosting, against MAGE-A3 and NYESO-1. Nonclinical data to support the rationale for enhanced CHAdOx1-MVA efficacy, in combination with chemo- and immunotherapy, has been generated in an in vivo surrogate model ( McAuliffe J et al, 2021 ). The MAGE-A3 antigen is expressed on tumours of a high percentage of cancer patients including non-small cell lung cancer (NSCLC). NYESO-1, expressed on a subset of MAGE-A3⁺ tumours, has the additional advantage of being highly immunogenic in cancer patients, either spontaneously or in response to peptide vaccination. The safety, tolerability, efficacy and immunogenicity of ChAdOx delivery of MAGE-A3/NYESO-1 antigens, boosted by MVA-MAGE-A3 (MAGE-A3⁺ pts) or MVA-MAGE-A3 and MVA-NYESO-1 (MAGE-A3⁺NYESO-1⁺ pts) are explored in this trial.

Trial design

This is a multi-centre, first-in-human, phase I/IIa, randomised, open label trial, run in the UK, for patients scheduled to receive first-line chemo-immunotherapy containing pembrolizumab as standard of care (SoC) treatment, for Stage III/IV NSCLC (and potentially additional indications) expressing MAGE-A3 +/- NYESO-1 (NCT04908111). Patients receive trial vaccination from Cycle 3 of their SoC treatment. In the initial Safety Run-In Stage, opened in October 2021, all patients receive ChAdOx1-MAGE-A3-NYESO prime vaccination and either MVA-MAGE-A3 single boost (3 evaluable pts) or MVA-MAGE-A3 and MVA-NYESO double boost (3 evaluable pts) vaccinations with SoC. The currently expanding Rolling Recruitment Stage includes a NSCLC Randomised Cohort of approximately 80 pts, randomised 1:1 to addition of vaccination. The primary objective is safety and tolerability, with key secondary objectives of immunogenicity and clinical efficacy. Tertiary objectives include correlative translational analyses.

Clinical trial identification

CRUKD/20/001, Release date: 07 Dec 2020.

Editorial acknowledgement

Legal entity responsible for the study

Cancer Research UK Centre for Drug Development.

Funding

Has not received any funding.

Disclosure

F. Blackhall: Financial Interests, Personal, Invited Speaker, Educational Symposium lecture: AstraZeneca; Financial Interests, Personal, Advisory Board, NTRK Advisory Board and guidelines for diagnosis: Bayer; Financial Interests, Personal, Other, IDMC Chair: AstraZeneca; Financial Interests, Personal, Advisory Board, Small cell Advisory Board Oct 2020 : Amgen; Financial Interests, Personal, Invited Speaker, ESMO Satellite Symposium November 2020 : Takeda; Financial Interests, Personal, Other, Consultancy for RETinhibitor development: Blueprint; Financial Interests, Personal, Other, Real world evidence research study design and analysis (EGFR): Janssen; Financial Interests, Institutional, Coordinating PI, Institutional payment for clinical trial activities: Amgen, Pfizer; Financial Interests, Institutional, Coordinating PI, Payment for clinical trial activities: Mirati; Financial Interests, Institutional, Coordinating PI, Clinical trial activities: BMS; Financial Interests, Institutional, Funding, Real world evidence research programme: Roche; Non-Financial Interests, Advisory Role, Application of genotyping platforms in lung cancer: Guardant Health; Non-Financial Interests, Advisory Role, Clinical trials of IMPs in lung cancer and translational lung cancer biomarkers: AstraZeneca. M. Marshall: Financial Interests, Personal and Institutional, Full or part-time Employment: Vaccitech plc Limited. P. Motteram: Financial Interests, Personal and Institutional, Financially compensated role: Vaccitech plc. B.J. van den Eynde: Financial Interests, Institutional, Advisory Role: Ludwig Institute for Cancer Research UK. C. Leung: Financial Interests, Institutional, Advisory Role: Ludwig Institute for Cancer Research UK. A. Hill: Financial Interests, Personal and Institutional, Other, Founder of Vaccitech plc: Oxford University. J. Spicer: Financial Interests, Institutional, Advisory Board, Compensation to my employer for time providing advice: Lilly, AstraZeneca, BMS, GSK, RS Oncology; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Institutional, Local PI, Reimbursement for treatment of patients in trial: Achilles, Genmab, Roche, Seattle Genetics, Trizell, BergenBio, MSD, Gilead; Financial Interests, Institutional, Coordinating PI, Reimbursement for treatment of patients in trial: Starpharma, BMS, IO Biotech, RS Oncology; Non-Financial Interests, Member of Board of Directors, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Member of Board of Directors, Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Advisory Role, Advice on licensing decisions for MHRA: CHM Expert Advisory Group on Oncology & Haematology. S.N. Symeonides: Financial Interests, Institutional, Advisory Board: Ellipses, Vaccitech, Medannex, EUSA, Eisai, MSD, BMS, Pfizer, Merck Serono, Duke Street Bio; Financial Interests, Institutional, Research Grant: MSD, Verastem; Financial Interests, Institutional, Coordinating PI: MSD, BioNTech, Nouscom; Financial Interests, Institutional, Local PI: Roche, Nucana, Sapience Therapeutics, BioLineRx, Boston Pharmaceuticals, Sierra Oncology, Incyte; Financial Interests, Institutional, Steering Committee Member: Scancell; Other, Conference attendance (no personal gain): Ipsen, BMS, EUSA, MSD. All other authors have declared no conflicts of interest.