Trial Title:
A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1
NCT ID:
NCT04908111
Condition:
Non-small Cell Lung Cancer (NSCLC)
Esophageal Neoplasms
Conditions: Official terms:
Lung Neoplasms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Esophageal Neoplasms
Conditions: Keywords:
Immunotherapy
Vaccine
Cancer
Oncology
Lung Cancer
NSCLC Non-small cell lung cancer
Esophageal neoplasms
Neoplasms, Squamous Cell
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Suspended
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
ChAdOx1-MAGEA3-NYESO
Description:
Patients commence their Standard of Care (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)
Arm group label:
Arm A: Trial vaccines with standard of care treatment
Arm group label:
Safety Run In
Arm group label:
Squamous Oesophageal Cancer Cohort
Intervention type:
Biological
Intervention name:
MVA-MAGEA3
Description:
Patients commence their Standard of Care (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)
Arm group label:
Arm A: Trial vaccines with standard of care treatment
Arm group label:
Safety Run In
Arm group label:
Squamous Oesophageal Cancer Cohort
Intervention type:
Combination Product
Intervention name:
Standard of care treatment
Description:
Patients will continue to receive standard of care treatment (chemotherapy and checkpoint
inhibitor).
Arm group label:
Arm B: Standard of care treatment
Intervention type:
Biological
Intervention name:
MVA-NYESO
Description:
Patients commence their Standard of Care (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)
Arm group label:
Arm A: Trial vaccines with standard of care treatment
Arm group label:
Safety Run In
Arm group label:
Squamous Oesophageal Cancer Cohort
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 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. 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.
2. 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 standard of care 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 standard of care at the time of enrolment.
3. 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.
1. 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.
2. 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.
4. 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.
5. Confirmed PD-L1 status (tumour proportion score) for NSCLC patients. Or a confirmed
PD-L1 combined positive score (CPS) for patients with squamous oesophageal cancer.
6. Archival tumour tissue or new biopsy expressing MAGE-A3 as demonstrated by RT-qPCR.
7. Life expectancy of at least 12 weeks.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Haematological and biochemical indices within the ranges shown below. These
measurements should be performed to confirm the patient's eligibility.
Haemoglobin (Hb) ≥90 g/L
Absolute neutrophil count (ANC) ≥1.5×10^9/L (growth factor support (G-CSF) is
allowed when used as part of routine supportive therapy for Standard of Care)
Platelet count ≥100×10^9/L
International normalized ratio (INR) AND prothrombin time (PT) OR Activated partial
thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant
therapy as long asINR or PT/ aPTT is within therapeutic range of intended use of
anticoagulants
Bilirubin ≤1.5 x upper limit of normal (ULN) OR < 3 x ULN in the presence of
documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR
≤5.0 x ULN in presence of liver metastases
Calculated creatinine clearance (using the Cockcroft & Gault [C&G] formula) ≥50
mL/min or serum creatinine ≤1.5 x UL
10. Aged 18 years or over at the time pre-screening consent is given.
Exclusion Criteria
1. 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.
2. 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.
3. 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.
4. 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.
5. 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 six
months afterwards.
6. 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.
7. 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 (CI)
and Sponsor agree would not compromise patient safety on trial are eligible.
8. Electrocardiogram (ECG) with clinically significant abnormalities or with QTcF
interval (QT corrected using Fridericia's formula) >480 msec.
9. At high medical risk because of non-malignant systemic disease including active
uncontrolled infection.
10. Historically known to be serologically positive for hepatitis B or human
immunodeficiency virus (HIV). Patients with previous Hepatitis C exposure but no
current infection are eligible to participate.
11. Has an active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
12. Has received COVID-19 Vaccine AstraZeneca (previously named AZD1222 or
ChAdOx1-nCoV-19) vaccine within six weeks of commencing chemotherapy and an immune
checkpoint inhibitor.
13. Has received any other live vaccination within four weeks before enrolment or
randomisation to the trial. Examples of live vaccines include, but are not limited
to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies,
Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not
allowed.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study drug. Use of
short (<7 day) courses of steroids as part of the SoC treatment management is
allowed.
15. Has undergone prior allogeneic hematopoietic stem cell transplantation within the
last 5 years. Participants who have had a transplant greater than 5 years ago are
eligible as long as there are no symptoms of graft versus host disease (GVHD).
16. Has previously experienced severe hypersensitivity (greater than or equal to Grade
3) to an immune checkpoint inhibitor, ChAdOx1 or MVA vaccines and/or any of their
excipients.
17. History of a severe allergy to eggs or history of severe allergic reaction to any
previous vaccination.
18. History of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2).
19. History of Capillary Leak Syndrome.
20. Is a participant or plans to participate in another interventional clinical trial,
whilst taking part in this Phase I/IIa trial. Participation in an observational
trial or interventional clinical trial which does not involve administration of an
IMP and which would not place an unacceptable burden on the patient in the opinion
of the Investigator and Medical Advisor would be acceptable.
21. Any other condition, which in the Investigator's opinion, would not make the patient
a good candidate for the clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Queen Elizabeth Hospital Birmingham
Address:
City:
Birmingham
Country:
United Kingdom
Facility:
Name:
Blackpool Victoria Hospital
Address:
City:
Blackpool
Country:
United Kingdom
Facility:
Name:
Ninewells Hospital
Address:
City:
Dundee
Country:
United Kingdom
Facility:
Name:
The Beatson West of Scotland Cancer Centre
Address:
City:
Glasgow
Country:
United Kingdom
Facility:
Name:
St James's University Hospital
Address:
City:
Leeds
Country:
United Kingdom
Facility:
Name:
Leicester Royal Infirmary
Address:
City:
Leicester
Country:
United Kingdom
Facility:
Name:
Clatterbridge Cancer Centre
Address:
City:
Liverpool
Country:
United Kingdom
Facility:
Name:
Guy's and St Thomas' NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Country:
United Kingdom
Facility:
Name:
Royal Preston Hospital
Address:
City:
Preston
Country:
United Kingdom
Facility:
Name:
Weston Park, Sheffield
Address:
City:
Sheffield
Country:
United Kingdom
Facility:
Name:
Southampton General Hospital
Address:
City:
Southampton
Country:
United Kingdom
Start date:
December 8, 2021
Completion date:
December 2027
Lead sponsor:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
Barinthus Biotherapeutics
Agency class:
Industry
Source:
Cancer Research UK
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04908111
