A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1

NCT04908111 | Suspended Phase 1 DMC

• 2 other identifiers: CRUKD/20/0012019-003015-64
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 9

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).

Conditions

Non-small Cell Lung Cancer (NSCLC); Squamous Oesophageal Cancer

Keywords

Immunotherapy; Vaccine; Cancer; Oncology; Lung Cancer; NSCLC Non-small cell lung cancer; Esophageal neoplasms; Neoplasms, Squamous Cell

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of the trial vaccines with SoC treatment (chemotherapy and an immune checkpoint inhibitor).

  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).

  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).

Secondary Outcomes (4)

• 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.

• 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.

• 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.

• 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).

Study Arms (4)

Safety Run-In

EXPERIMENTAL

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.

Biological: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp); Biological: MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu); Biological: MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu)

NSCLC Arm A: Trial vaccines with SoC treatment

EXPERIMENTAL

Approximately 40 patients will be randomised to receive the trial vaccines with SoC treatment in this arm.

Biological: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp); Biological: MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu); Biological: MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu)

NSCLC Arm B: SoC treatment

OTHER

Approximately 40 patients will be randomised to receive SoC treatment alone in this arm.

Combination Product: Standard of care treatment

Squamous Oesophageal Cancer Cohort

EXPERIMENTAL

Approximately 17 patients with squamous oesophageal cancer will received the trial vaccines with SoC treatment

Biological: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp); Biological: MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu); Biological: MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu)

Interventions

ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) BIOLOGICAL

Patients commence their SoC chemotherapy in combination with an immune checkpoint inhibitor in 3 weekly cycles. Patients are screened during the first 2 cycles of SoC treatment to confirm eligibility for the trial. Patients who receive trial vaccines (safety run in stage, Arm A of the NSCLC randomisation cohort and Squamous Oesophageal Cancer Cohort) continue to receive their SoC treatment plus: * First prime ChAdOx1-MAGEA3-NYESO vaccine on Cycle 3 Day 1 of SoC treatment. * First boost MVA-MAGEA3 vaccine, and if applicable a first boost MVA-NYESO vaccine, 21 days later. * For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 15 weeks following first prime vaccine * Second boost MVA-MAGAE3 vaccine, and if applicable a second boost MVA-NYESO vaccine, 21 days following second prime vaccine Patients in Arm B of the NSCLC randomisation cohort will continue to receive their SoC treatment only throughout the trial (i.e. no trial vaccines)

NSCLC Arm A: Trial vaccines with SoC treatment; Safety Run-In; Squamous Oesophageal Cancer Cohort

MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu) BIOLOGICAL

Patients commence their SoC chemotherapy in combination with an immune checkpoint inhibitor in 3 weekly cycles. Patients are screened during the first 2 cycles of SoC treatment to confirm eligibility for the trial. Patients who receive trial vaccines (safety run in stage, Arm A of the NSCLC randomisation cohort and Squamous Oesophageal Cancer Cohort) continue to receive their SoC treatment plus: * First prime ChAdOx1-MAGEA3-NYESO vaccine on Cycle 3 Day 1 of SoC treatment. * First boost MVA-MAGEA3 vaccine, and if applicable a first boost MVA-NYESO vaccine, 21 days later. * For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 15 weeks following first prime vaccine * Second boost MVA-MAGAE3 vaccine, and if applicable a second boost MVA-NYESO vaccine, 21 days following second prime vaccine Patients in Arm B of the NSCLC randomisation cohort will continue to receive their SoC treatment only throughout the trial (i.e. no trial vaccines)

NSCLC Arm A: Trial vaccines with SoC treatment; Safety Run-In; Squamous Oesophageal Cancer Cohort

Standard of care treatment COMBINATION_PRODUCT

Patients will continue to receive SoC treatment (chemotherapy and checkpoint inhibitor).

NSCLC Arm B: SoC treatment

MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu) BIOLOGICAL

Patients commence their SoC chemotherapy in combination with an immune checkpoint inhibitor in 3 weekly cycles. Patients are screened during the first 2 cycles of SoC treatment to confirm eligibility for the trial. Patients who receive trial vaccines (safety run in stage, Arm A of the NSCLC randomisation cohort and Squamous Oesophageal Cancer Cohort) continue to receive their SoC treatment plus: * First prime ChAdOx1-MAGEA3-NYESO vaccine on Cycle 3 Day 1 of SoC treatment. * First boost MVA-MAGEA3 vaccine, and if applicable a first boost MVA-NYESO vaccine, 21 days later. * For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 15 weeks following first prime vaccine * Second boost MVA-MAGAE3 vaccine, and if applicable a second boost MVA-NYESO vaccine, 21 days following second prime vaccine Patients in Arm B of the NSCLC randomisation cohort will continue to receive their SoC treatment only throughout the trial (i.e. no trial vaccines)

NSCLC Arm A: Trial vaccines with SoC treatment; Safety Run-In; Squamous Oesophageal Cancer Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written (signed and dated) informed consent for both pre-screening and the main trial and capable of co-operating with any investigational medicinal product (IMP) administration and follow-up.
• Histologically or cytologically proven Stage IIIB, IIIC or IV squamous NSCLC or Stage IIIB or IV non-squamous NSCLC scheduled to receive pembrolizumab and chemotherapy as SoC at the time of enrolment or randomisation. Patients can receive up to two cycles of SoC pembrolizumab in combination with chemotherapy prior to enrolment or randomisation to the trial.
• Or histologically proven inoperable Stage III or IV squamous cell carcinomas of the oesophagus or gastro-oesophageal junction (referred to as squamous oesophageal cancer) scheduled to receive or continue to receive chemotherapy and pembrolizumab as SoC at the time of enrolment.
• NSCLC patients with no prior immune checkpoint inhibitor therapy prior to the pembrolizumab they are receiving in combination with chemotherapy at time of enrolment or randomisation.
• For non-squamous NSCLC patients, the patient has not received previous systemic therapy for advanced/metastatic disease. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease.
• For squamous NSCLC patients, the patient has not received previous cytotoxic chemotherapy for advanced/metastatic disease. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease.
• Or patients with squamous oesophageal cancer with no prior systemic therapy for advanced disease and with no prior immune checkpoint inhibitor therapy prior to the chemotherapy and immune checkpoint inhibitor they are receiving at time of enrolment to the trial. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease.
• Have at least one measurable lesion according to RECIST v1.1. Note: A measurable lesion may be biopsied at screening and on trial, however that lesion cannot be selected as a target lesion for disease assessment according to RECIST v1.1.
• Confirmed PD-L1 status (tumour proportion score) for NSCLC patients. Or a confirmed PD-L1 combined positive score for patients with squamous oesophageal cancer.
• Archival tumour tissue or new biopsy expressing MAGE-A3 as demonstrated by quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR).
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.
• Haemoglobin ≥90 g/L
• Absolute neutrophil count ≥1.5×10\^9/L (growth factor support Granulocyte-Colony Stimulating Factor is allowed when used as part of routine supportive therapy for SoC)

You may not qualify if:

• For non-squamous NSCLC patients, patients who have received previous systemic therapy for advanced/metastatic disease prior to the pembrolizumab they are receiving in combination with chemotherapy at time of enrolment or randomisation. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease. Palliative radiotherapy is allowed. Irradiated lesions will not be evaluable for response.
• For squamous NSCLC patients, patients who have received previous cytotoxic chemotherapy for advanced/metastatic disease prior to the pembrolizumab they are receiving in combination with chemotherapy at time of enrolment or randomisation. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease. Palliative radiotherapy is allowed. Irradiated lesions will not be evaluable for response.
• Or for patients with squamous oesophageal cancer - patients who have previously received systemic therapy for advanced disease and with no prior immune checkpoint inhibitor therapy prior to the SoC treatment outlined in this clinical trial. Completion of treatment for earlier stage disease with chemotherapy with or without radiotherapy as part of neoadjuvant/radical/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of recurrent locally advanced or metastatic disease. Palliative radiotherapy is allowed. Irradiated lesions will not be evaluable for response.
• Previous therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., anti-CTLA-4, OX 40, anti-CD137). This does not include the immune checkpoint inhibitor patients receive in combination with chemotherapy commencing during screening prior to enrolment or randomisation to the trial.
• Current or prior malignancy which could affect safety or efficacy assessment of the IMP or compliance with the protocol or interpretation of results. Patients with curatively-treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinomas-in-situ are eligible.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with symptomatically active brain metastases or leptomeningeal metastases. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Women of child-bearing potential (or are already pregnant or lactating). However, those patients who meet the following points are considered eligible:
• Have a negative serum or urine pregnancy test before enrolment or randomisation and;
• Agree to use two forms of contraception (one effective form plus a barrier method) \[oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom\] or agree to sexual abstinence, effective from the first administration of ChAdOx1-MAGEA3-NYESO, throughout the treatment phase of the trial and for 6 months afterwards.
• Male patients with partners of child-bearing potential. However, those patients who meet the following points are considered eligible:
• They agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence effective from the Cycle 3 Day 1 of SoC treatment, throughout the treatment phase of the trial and for six months afterwards.
• Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intra-uterine device, diaphragm with spermicidal gel or sexual abstinence.
• Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
• Major thoracic or abdominal surgery from which the patient has not yet recovered. Patients who have undergone other types of surgery which the Chief Investigator and Sponsor agree would not compromise patient safety on trial are eligible.
• Electrocardiogram (ECG) with clinically significant abnormalities or with QTcF interval (QT corrected using Fridericia's formula) \>480 msec.

Sponsors & Collaborators

• Cancer Research UK: lead
• Vaccitech Oncology Ltd (VOLT): collaborator

Study Sites (9)

Blackpool Victoria Hospital

Blackpool, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Royal Preston Hospital

Preston, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Lung Neoplasms; Esophageal Neoplasms; Neoplasms, Squamous Cell

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Fiona Blackhall, Prof

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: June 1, 2021
• Study Start: October 15, 2021
• Primary Completion: September 18, 2024
• Study Completion (Estimated): March 6, 2029
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: All requests made within 5 years from the end of trial will be considered; requests made subsequently will be considered where possible.
• Access Criteria: Researchers who are funded or employed by Cancer Research UK whose proposed use of the data is approved by a review committee of CDD.

Locations

GB (9)