Phase 1 study of NG-350A plus pembrolizumab in metastatic or advanced epithelial tumours
| ISRCTN | ISRCTN94964671 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN94964671 |
| EudraCT/CTIS number | 2022-000335-22 |
| IRAS number | 1005052 |
| ClinicalTrials.gov number | NCT05165433 |
| Secondary identifying numbers | NG-350A-02, IRAS 1005052, CPMS 52187 |
- Submission date
- 09/02/2022
- Registration date
- 17/06/2022
- Last edited
- 04/07/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
This study will evaluate the safety (side effects), how the body processes the treatment (pharmacokinetics), and what the treatment does to the body (pharmacodynamic effects) of the drugs NG-350A plus pembrolizumab in patients with cancer.
Worldwide, almost 10 million deaths in 2020 were estimated to be due to cancer. Despite the introduction of multiple new therapies, the overall burden of cancer incidence and mortality is growing worldwide and there remains a critical need for new and effective treatments.
NG-350A is an experimental gene therapy medicinal product.
The other drug used in this study, pembrolizumab, works by changing the action of the immune system, directing it to attack cancer cells. Pembrolizumab belongs to a class of drugs known as monoclonal antibodies. Pembrolizumab is approved for use in the UK.
Who can participate?
Patients over 18 years, with one of the types of cancer being investigated.
What does the study involve?
The study will be conducted with participants in 2 phases. Phase 1a will investigate NG-350A administration by intravenous (IV) infusion in combination with fixed-dose pembrolizumab in a range of tumour types. Phase 1b will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in phase 1a.
What are the possible benefits and risks of participating?
Benefits:
There will be no direct medical benefit, we hope the information learned from this study will benefit other participants with cancer in the future.
Risks:
It is not possible to predict all side-effects but based on prior studies/literature. Kidney damage, breathing problems, intestinal blockages, abnormal blood clotting tests (not associated with bleeding/clotting) and cytokine release syndrome (see ICF) are considered important risks in this study. Successful mitigation strategies have been established to reduce the risk of these side-effects (eg not enrolling patients most at risk, extra monitoring & modifying dosing schedules). Pembrolizumab is approved for treating the cancer types in this study; further unknown risks may occur when it is combined with NG-350A. Prior studies with related viral vectors + pembrolizumab have not identified new risks. A complete list of potential risks and side-effects are provided in the ICF. Patients will be closely monitored during the study and if the patient’s condition worsens or disease progression occurs, study treatment will be discontinued. As relatively frequent visits are required, visit windows are in place to allow patients to attend at the most convenient times for them; some visits may be by phone. Patients need to have routine blood draws (max 122 mL drawn per visit), CT or MRI scans and biopsies. These are all common procedures which would likely be carried out as part of the patient’s routine care. All procedures will be carried out by trained professionals. Biopsies can cause pain and so the area to be biopsied is numbed with a local anaesthetic and painkillers may be prescribed. The effect of NG-350A on babies before they are born, or on breastfeeding children is not known. Patients who are pregnant, planning pregnancy or are breastfeeding, will not be included in the study. A number or requirements are in place to prevent pregnancy.
Where is the study run from?
PsiOxus Therapeutics Ltd. (UK)
When is the study starting and how long is it expected to run for?
February 2022 to June 2026
Who is funding the study?
PsiOxus Therapeutics Ltd (UK)
Who is the main contact?
Pia Donaldson, IRASprojectdeputy@psioxus.com
Contact information
Scientific
PsiOxus House
4-10 The Quadrant
Barton Lane
Abingdon
OX14 3YS
United Kingdom
| Phone | +44 7572 102367 |
|---|---|
| andrew.fox@psioxus.com |
Scientific
PsiOxus House
4-10 The Quadrant
Barton Lane
Abingdon
OX14 3YS
United Kingdom
| Phone | +44 1235 835328 |
|---|---|
| irasprojectdeputy@psioxus.com |
Principal Investigator
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
| Phone | +44 7966770228 |
|---|---|
| eileen.parkes@ouh.nhs.uk |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Treatment |
| Scientific title | A multicentre, open-label, non-randomized, phase 1a/1b study of NG-350A, a tumour-selective anti-CD40-expressing adenoviral vector in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours |
| Study objectives | 1. To characterise the safety and determine the recommended dose of NG-350A in combination with pembrolizumab in patients with advanced cancers 2. Explore the efficacy, distribution and immune response of NG-350A in combination with pembrolizumab in patients with advanced cancers |
| Ethics approval(s) | Approval pending, London - West London & GTAC (London), ref: 22/LO/0161 |
| Health condition(s) or problem(s) studied | Advanced cancer |
| Intervention | This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-350A in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours. Phase 1a will investigate NG-350A administration by intravenous (IV) infusion in combination with fixed-dose pembrolizumab in a range of tumour types. Phase 1b will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in phase 1a. The estimated duration of the study from enrolment to follow-up is 112 weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | NG-350A, pembrolizumab |
| Primary outcome measure | 1. Incidence of: adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation of study treatment or study discontinuation and AEs resulting in death measured continuously, up to 100 days after last dose of study 2. Incidence of abnormalities in vital signs or other clinical safety assessments measured continuously, up to 100 days after last dose of study treatment 3. Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria measured continuously during DLT period |
| Secondary outcome measures | Measured at 26 and 52 weeks, and at study end (other timepoints may be utilized): 1. ORR, DCR and DoR according to Investigator (phase 1a) and IRRC (phase 1b) assessment, and using RECIST v1.1 and immune iRECIST measured using the number and percentage of patients who achieve either a CR or PR according to Investigator or IRRC (phase 1b only) assessments from the date of first dose of study treatment to the end of the study. 2. Median PFS and PFS rates according to Investigator (phase 1a) and IRRC assessments (phase 1b) measured using median PFS and PFS rates measured according to Investigator (phase 1a) and IRRC assessments (phase 1b) at weeks 26 and 52 3. OS rate defined as the interval between the day of the first dose of study treatment until the date of death due to any cause. 4. Measurements of NG-350A pharmacokinetics/blood concentrations of NG-350A measured using blood samples taken immediately after the end of infusion. 5. Measurements of NG-350A immunogenicity/anti-NG-350A antibody titres measured using blood samples taken at the timepoints defined in the schedule of assessments. |
| Overall study start date | 04/02/2022 |
| Completion date | 01/06/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 198 |
| Key inclusion criteria | 1. Provide written informed consent to participate 2. Aged 18 years or over on day of signing informed consent 3. Patients must have one of eleven histologically or cytologically confirmed metastatic/advanced carcinomas or adenocarcinomas that has progressed after at least one line of systemic therapy and are incurable by local therapy 4. At least one measurable site of disease according to RECIST v1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area 5. Prior treatment with a PD-1/PD-L1 inhibitor (prior PD-1/PD-L1 may have been given as monotherapy or combination therapy) 6. Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies 7. Ability to comply with study procedures in the Investigator’s opinion 8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 |
| Key exclusion criteria | 1. Prior or planned allogeneic or autologous bone marrow or tissue/organ transplantation 2. Splenectomy 3. Active infections requiring systemic anti-infective treatment, physician monitoring/hospital admission or recurrent fevers (>38.0˚C) associated with a clinical diagnosis of active infection within 20 days of the anticipated first dose of study drug. Patients who have had an active infection requiring systemic therapy, but not hospital admission, which has resolved at least 10 days before the anticipated first dose of study drug are eligible 4. Treatment with the antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 10 days prior to the first dose of study treatment; or pegylated interferon in the 4 weeks before the first dose of study treatment 5. Known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Known history of HIV infection (no testing for HIV, hepatitis B or hepatitis C is required unless mandated by local health authority) 6. Patients who have active autoimmune disease that has required systemic therapy in the past 2 years, are immunocompromised in the opinion of the Investigator, or are receiving chronic systemic immunosuppressive treatment (including steroid therapy in doses exceeding 10 mg daily of prednisone equivalent) 7. Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before first dose of study drug |
| Date of first enrolment | 01/04/2022 |
| Date of final enrolment | 01/06/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
- United States of America
Study participating centres
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Clatterbridge Road
Wirral
CH63 4JY
United Kingdom
Suite 540
Santa Monica, CA
90404
United States of America
515 Holcombe Blvd
Houston, TX
77030-4009
United States of America
Sponsor information
Industry
PsiOxus House
4-10 The Quadrant
Barton Lane
Abingdon
OX14 3YS
England
United Kingdom
| Phone | +44 1235 835328 |
|---|---|
| clinical.operations@psioxus.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Other publication Submission to regulatory authorities All participants' data will be anonymised at clinical sites. Explicit consent for the processing of personal data will be obtained from the participants before the collection of data. Such consent will also address the future use of data, and transfer of data to other entities and countries outside the EU which may not protect privacy to the same extent as European law. All data generated during the study will be archived securely by the Sponsor in line with local regulatory requirements. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/07/2022: Internal review.
09/02/2022: Trial's existence confirmed by NHS HRA.
