A Cancer Research UK Phase I/IIa Trial of Chimpanzee Adenovirus Oxford 1 (ChAdOx1) and Modified Vaccinia Ankara (MVA) Vaccines Against MAGE-A3 and NY-ESO-1 With Standard of Care Treatment (Chemotherapy and an Immune Checkpoint Inhibitor)

Plain English Summary

A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1 is a Phase 2 clinical trial sponsored by Cancer Research UK studying Non-small Cell Lung Cancer (NSCLC), Squamous Oesophageal Cancer. This trial tests two experimental vaccines (ChAdOx1 and MVA) designed to help the immune system fight specific types of lung and esophageal cancer. It is for patients with advanced non-small cell lung cancer (NSCLC) or squamous esophageal cancer who are already receiving standard chemotherapy and an immune checkpoint inhibitor. Participation involves receiving the standard treatment along with the two trial vaccines, with regular check-ups and tests. Alternative treatments include standard chemotherapy and immune checkpoint inhibitors, or other clinical trials. The trial aims to enroll 15 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with advanced non-small cell lung cancer (NSCLC) or squamous esophageal cancer. Must have specific tumor markers (MAGE-A3 expression) and PD-L1 status. Must be 18 years or older and have a life expectancy of at least 12 weeks. Cannot have received prior treatment with immune checkpoint inhibitors for advanced disease (with some exceptions for specific cancer types). This trial is studying Non-small Cell Lung Cancer (NSCLC), Squamous Oesophageal Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how safe and well-tolerated the new vaccines are when given with standard treatment, meaning doctors will closely monitor for any side effects. The specific primary outcome measures are: 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 5 years).). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment for lung and esophageal cancers by using vaccines to boost the immune system's attack on cancer cells, addressing a need for more effective therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer (NSCLC), Squamous Oesophageal Cancer, where improved treatment options are needed.

Investor Insight

This trial, though suspended, explores novel vaccine combinations for difficult-to-treat cancers, indicating potential future market opportunities in immunotherapy if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of the trial vaccines, and how they might interact with your current treatment. Be prepared for regular clinic visits for vaccine administration, blood tests, and scans to monitor your cancer and any side effects. Understand that the trial is currently suspended, which may affect its availability and timeline. The trial is being conducted at 9 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 15 participants

Interventions

• BIOLOGICAL: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) — 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 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 pri
• BIOLOGICAL: MVA-MAGEA3 (Route = IM injection, Dose = 1.3×10^8 pfu) — 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 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 pri
• COMBINATION_PRODUCT: Standard of care treatment — Patients will continue to receive SoC treatment (chemotherapy and checkpoint inhibitor).
• BIOLOGICAL: MVA-NYESO (Route = IM injection, Dose = 1.5×10^8 pfu) — 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 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 pri
• BIOLOGICAL: Biological/Vaccine: ChAdOx1-MAGEA3-NYESO (Route = IM injection, Dose = 5×10^10 vp) — 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 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 MVA-NYESO vaccine, 21 days later. •For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 1

Primary Outcomes

• 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 5 years).)

Secondary Outcomes

• 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).)
• 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).)
• 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).)
• 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).)

Full 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 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.
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 for patients with squamous oesophageal cancer.
6. Archival tumour tissue or new biopsy expressing MAGE-A3 as demonstrated by quantitative Reverse Transcription Polymerase Chain Reaction (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 ≥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)

   Platelet count ≥100×10\^9/L

   International normalized ratio (INR) ≤1.5\* AND prothrombin time (PT) OR Activated partial thromboplastin time (aPTT) ≤1.5\* × Upper Limit of Normal (ULN) \*unless participant is receiving anticoagulant therapy as long as INR or PT/aPTT is within therapeutic range of intended use of anticoagulants.

   Bilirubin ≤1.5 × ULN OR \<3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia)

   Alanine aminotransferase or aspartate aminotransferase ≤3.0 × ULN OR ≤5.0 × ULN in presence of liver metastases

   Calculated creatinine clearance (using the Cockcroft \& Gault \[C\&G\] formula) ≥50 mL/min or serum creatinine ≤1.5 × ULN
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 ar

Trial Locations

• 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

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Esophageal Cancer
• Gastroesophageal Junction Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Squamous Cell Carcinoma
• Metastatic Cancer
• Advanced Cancer
• Immunotherapy
• Cancer Vaccines
• Oncology

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