A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1
- Conditions
- Non-small Cell Lung Cancer (NSCLC)Squamous Oesophageal Cancer
- Interventions
- Biological: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp)Combination Product: Standard of care treatmentBiological: MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu)Biological: MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu)
- Registration Number
- NCT04908111
- Lead Sponsor
- Cancer Research UK
- Brief Summary
This clinical trial is looking at two new vaccines called ChAdOx1-MAGEA3-NYESO, MVA-MAGEA3 and MVA-NYESO given with patients' standard of care treatment (chemotherapy and an immune checkpoint inhibitor).
- Detailed Description
Patients with non-small cell lung cancer (NSCLC) or squamous oesophageal cancer will be entered into the trial as these tumour types are commonly known to have MAGE-A3 and NY-ESO-1 proteins on their cancer cells. The vaccines contain harmless parts of these proteins allowing them to show these proteins to the immune system. It is expected the immune system will 'learn' that these proteins are foreign to the body. The immune system should then attack the proteins on the cancer cells, killing them. It is expected the vaccines will help the chemotherapy and immune checkpoint inhibitor to work better.
This is a first-in-human clinical trial which has two stages:
* A 'Safety Run In' stage where six evaluable patients will receive the trial vaccines with standard of care treatment to confirm they are safe before opening the next stage.
* A 'Rolling Recruitment' stage consisting of two cohorts:
1. NSCLC Randomisation Cohort of approximately 80 patients with NSCLC will be randomly allocated by computer (randomised) to one of two groups (arms). Patients in Arm A will receive the vaccines with their standard of care treatment and patients in Arm B will continue with their standard of care treatment alone. There is a 1 in 2 chance patients will receive the vaccines.
2. Squamous Oesophageal Cancer Cohort: Approximately 17 patients with squamous oesophageal cancer will be recruited to receive trial vaccines with their standard of care treatment.
The main aims of the trial are to find out:
* More about potential side effect of the vaccine and how they can be managed.
* Whether the vaccines with standard of care treatment are better at shrinking NSCLC than just the standard of care treatment alone.
* What happens to the vaccines inside the body.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Safety Run-In ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) Six evaluable patients will receive the trial vaccines with Standard of Care (SoC) treatment to confirm they are safe before opening the next stage of the trial. These patients will not be randomised. Safety Run-In MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu) Six evaluable patients will receive the trial vaccines with Standard of Care (SoC) treatment to confirm they are safe before opening the next stage of the trial. These patients will not be randomised. Safety Run-In MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu) Six evaluable patients will receive the trial vaccines with Standard of Care (SoC) treatment to confirm they are safe before opening the next stage of the trial. These patients will not be randomised. NSCLC Arm A: Trial vaccines with SoC treatment ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) Approximately 40 patients will be randomised to receive the trial vaccines with SoC treatment in this arm. NSCLC Arm A: Trial vaccines with SoC treatment MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu) Approximately 40 patients will be randomised to receive the trial vaccines with SoC treatment in this arm. NSCLC Arm A: Trial vaccines with SoC treatment MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu) Approximately 40 patients will be randomised to receive the trial vaccines with SoC treatment in this arm. NSCLC Arm B: SoC treatment Standard of care treatment Approximately 40 patients will be randomised to receive SoC treatment alone in this arm. Squamous Oesophageal Cancer Cohort ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) Approximately 17 patients with squamous oesophageal cancer will received the trial vaccines with SoC treatment Squamous Oesophageal Cancer Cohort MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu) Approximately 17 patients with squamous oesophageal cancer will received the trial vaccines with SoC treatment Squamous Oesophageal Cancer Cohort MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu) Approximately 17 patients with squamous oesophageal cancer will received the trial vaccines with SoC treatment
- Primary Outcome Measures
Name Time Method To assess the safety and tolerability of the trial vaccines with SoC treatment (chemotherapy and an immune checkpoint inhibitor). From time of written consent to participate in the trial until the End of Treatment visit for each patient. Any trial vaccine-related serious adverse events that become known after this period will be reported up to the end of trial (Max 89 Months). Incidence of adverse events (including injection site reactions and toxicity), including relatedness, seriousness and severity (graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version 5.0).
- Secondary Outcome Measures
Name Time Method To determine the efficacy (Progression Free Survival [PFS], in months) of the trial vaccines when given with SoC treatment (chemotherapy and immune checkpoint inhibitor). Until end of efficacy and survival follow-up (Max 5 years) for non-vaccinated patients and end of extended follow-up (Max 89 months) for vaccinated patients. PFS will be assessed as time from Cycle 3 Day 1 of SoC treatment to the date of disease progression. using Response Evaluation Criteria in Solid Tumours (RECIST) and immune RECIST (iRECIST).
To determine the efficacy (Overall Response Rate [ORR], in months) of the trial vaccines when given with SoC treatment (chemotherapy and immune checkpoint inhibitor). Until end of efficacy and survival follow-up (max 5 years) for non-vaccinated patients and end of extended follow-up (Max 89 months) for vaccinated patients. ORR will be reported as the number of randomised patients who have achieved a complete response or partial response.
To determine the efficacy (Overall Survival [OS], in months) of the trial vaccines when given with SoC treatment (chemotherapy and immune checkpoint inhibitor). Until end of efficacy and survival follow-up (Max 5 years) for non-vaccinated patients and end of extended follow-up (Max 89 months) for vaccinated patients. OS will be assessed as time from Cycle 3 Day 1 of SoC treatment to the date of death from any cause.
To determine the immunogenicity (antigen-specific peripheral response) of the trial vaccines given with SoC treatment (chemotherapy and an immune checkpoint inhibitor). Screening (prior to commencing SoC treatment, Cycle 3 Day 1 (each cycle is 21 days), Cycle 3 Day 15/2 weeks after ChAdOx1-MAGEA3-NYESO vaccination, Cycle 4 Day 1, Cycle 4 Day 7/1 week after MVA vaccination and at End of Treatment visit (Max 40 weeks). Percentage of patients showing peripheral immune response. Immunological response will be measured in patient blood by antigen-specific T cells by ex vivo ELISpot assay.
Trial Locations
- Locations (9)
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Blackpool Victoria Hospital🇬🇧Blackpool, United Kingdom