ADVANCE

RGEA, University of Oxford

Churchill hospital, Old Road, Headington, Oxford, United Kingdom, OX3 7LE

Adrian Hill, The Jenner Institute, University of Oxford, +44 1865617610, adrian.hill@ndm.ox.ac.uk

Adrian Hill, The Jenner Institute, University of Oxford, +44 1865617610, adrian.hill@ndm.ox.ac.uk

No

No

No

Final

20 May 2022

Yes

20 May 2022

Yes

20 May 2022

Yes

To assess the safety and efficacy of ChAd-MVA 5T4 vaccination in combination with checkpoint inhibitor nivolumab when administered to early stage and advanced metastatic prostate cancer patients. Low- or intermediate-risk localised or locally advanced prostate cancer patients: • To assess safety of the viral vectored ChAd-MVA 5T4 vaccine when administered in combination with anti-PD-1 mAb • To determine whether ChAd-MVA 5T4 vaccine in combination with anti-PD-1 will impact on the serum level of PSA Metastatic prostate cancer patients • To assess safety of the viral vectored ChAd-MVA 5T4 vaccine when administered in combination with anti-PD-1 mAb • To assess efficacy of the viral vectored ChAd-MVA 5T4 vaccine when administered in combination with anti-PD-1 mAb as measured by composite response rate defined as one of the following: o reduction of circulating tumour DNA o serum PSA decrease

All patients will sign and date the informed consent form before any study-specific procedures are performed. The information sheet will be made available to the patient at least 24 hours prior to the screening visit. The patient will be fully informed of all aspects of the trial, the potential risks and their obligations. The following general principles will be emphasised: • Participation in the study is entirely voluntary • Refusal to participate involves no penalty or loss of medical benefits • The patient may withdraw from the study at any time • The patient is free to ask questions at any time to allow him or her to understand the purpose of the study and the procedures involved • The study involves research of an investigational vaccine and checkpoint inhibitor • The study involves delaying the patient’s surgery by approximately 2 months • There may be no direct benefit for participating The aims of the study and all tests to be carried out will be explained. The patient will be given the opportunity to ask about details of the study, and will then have time to consider whether or not to participate. If they do decide to participate, they will sign and date the consent form, which will also be signed and dated by the investigator. One copy will be given to the partiicpant, one copy will be placed in the study file, and the original will be placed in their medical notes.

01 Oct 2018

No

No

United Kingdom: 23

23

0

0

0

0

0

0

0

2

21

0

Whole trial (overall period)

Non-randomised - controlled

N/A

ChAdOx1.5T4 vaccine

Solution for injection

Injection , Intramuscular use

ChAdOx1.5T4 vaccine is is an unlicensed medicinal product manufactured by by the University of Oxford Clinical Biomanufacturing Facility (CBF), Churchill Hospital, Oxford. It is formulated in formulation buffer at a nominal concentration of 1.1x1011 vp/mL. The formulation buffer consists of 10mM Histidine, 7.5% sucrose, 35mM NaCI, 1mM MgCl2, 0.1% PS80, 0.1mM EDTA, 0.5% EtOH, pH 6.6. The fill volume is 0.5-1.0 mL. The dose of ChAdOx1.5T4 used in this study is 2.5x1010 vp. The vaccine was allowed to thaw to room temperature and were administered by intramuscular injection within 1 hour of removal from the freezer. The preferred site for vaccination was the vastus lateralis muscle of the thigh but the deltoid muscle of the arm was an acceptable alternative.

MVA.5T4 vaccine

Solution for injection

Injection , Intramuscular use

MVA.5T4 vaccine is an unlicensed medicinal product that has not been administered to humans before. It has been manufactured under Good Manufacturing Practice conditions by IDT Biologika GmbH, Germany. MVA.5T4 was supplied as a frozen liquid formulation in 10mM Tris buffer 140 mM NaCl, pH 7.7 in 2.0 mL clear glass vials. The formulation titre is 2x109 pfu/ml, the final drug product titre is 1x109pfu/ml. The fill volume is 0.55 mL. The vaccine was allowed to thaw to room temperature and administered by intramuscular injection within 1 hour of removal from the freezer. The preferred site for vaccination was the vastus lateralis muscle of the thigh but the deltoid muscle of the arm was an acceptable alternative. It was planned to use a different thigh (arm) for each of the two MVA.5T4 immunisations.

Immune checkpoint inhibitor nivolumab

Opdivo®

Concentrate for solution for infusion

Intravenous use

Nivolumab 480mg, was prepared from 10mg/ml concentrate, diluted into sodium chloride 9mg/mL (0.9%) solution for injection and administered intravenously in a volume of 100ml to a final concentration of 4.8mg/ml. Preparation and handling adopted strict aseptic technique. In line with the manufacturer’s instructions, nivolumab was administered intravenously over a period of 60 minutes using a volumetric pump, an infusion set and an in-line, sterile, nonpyrogenic, low protein binding filter of pore size of 0.2μm to 1.2μm. After administration the line was flushed with sodium chloride 9 mg/mL (0.9%) solution for injection.

Group 2

Group 2

The participant must satisfy all the following criteria to be eligible for the study: - Histologically confirmed adenocarcinoma of the prostate cancer. Note, any Gleason grade or primary tumour staging at diagnosis is permitted. - Evidence of at least one distant metastasis based on MRI, CT, PET or bone scintigraphy. - Established on and suitable to continue with androgen deprivation therapy (ADT) using any luteinizing hormone releasing hormone (LHRH) agonist. LHRH agonist therapy may include goserelin (Zoladex®), leuprorelin acetate (Prostap®) or any other licenced product in this class. - On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time of enrolment, defined according Prostate Cancer Working Group 3 Criteria as either: • PSA progression as defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screeni

Group 2

Group 2

The participant must satisfy all the following criteria to be eligible for the study: - Histologically confirmed adenocarcinoma of the prostate cancer. Note, any Gleason grade or primary tumour staging at diagnosis is permitted. - Evidence of at least one distant metastasis based on MRI, CT, PET or bone scintigraphy. - Established on and suitable to continue with androgen deprivation therapy (ADT) using any luteinizing hormone releasing hormone (LHRH) agonist. LHRH agonist therapy may include goserelin (Zoladex®), leuprorelin acetate (Prostap®) or any other licenced product in this class. - On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time of enrolment, defined according Prostate Cancer Working Group 3 Criteria as either: • PSA progression as defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screeni

Those participants who completed the full study

Primary

Week 48

How many had the dose(s) administered at each stage

Primary

Progression of vaccinations / infusions through the trial

From Enrolment until End of Study

ADV-00118011

26

Group 2