NCT04908111

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

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)

• Status: Suspended
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

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

Interventions

Type	Name	Description
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 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.
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 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.
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 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.
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 15 weeks following first prime vaccine. •Second boost MVA-MAGAE3 vaccine and a second boost MVA-NYESO vaccine, 21 days following second prime vaccine.
BIOLOGICAL	Biological/Vaccine: 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 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 a second boost MVA-NYESO vaccine, 21 days following second prime vaccine.
BIOLOGICAL	Biological/Vaccine: 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 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 a second boost MVA-NYESO vaccine, 21 days following second prime vaccine.
BIOLOGICAL	Biological/Vaccine: ChAdOx1-MAGEA3-NYESO (Route = intramuscular (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 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.
BIOLOGICAL	Biological/Vaccine: 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 21 days later. •For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 15 weeks following first prime vaccine and a second MVA-MAGEA3 boost vaccine 21 days after the second prime vaccine.

Timeline

• Start date: 2021-10-15
• Primary completion: 2024-09-18
• Completion: 2026-10-16
• First posted: 2021-06-01
• Last updated: 2026-04-06

Locations

9 sites across 1 country: United Kingdom