Metastatic CancerPhase 1NEBULANCT05043714
Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours
A Phase 1 study testing NG-641 in combination with Nivolumab in people with Metastatic Cancer and Epithelial Tumor, run by Akamis Bio at 6 sites in 2 countries.
Trial summary
This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination with nivolumab (or standard of care PD-1 inhibition) in patients with metastatic or advanced epithelial tumours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Epithelial Tumor
- What is being tested?
- NG-641 in combination with Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 1 Dec 2021to 4 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase 1a:
- Patients must have histologically or cytologically documented metastatic/advanced epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.
- At least one measurable site of disease according to RECIST Version 1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area
- Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
- All patients:
- Provide written informed consent to participate
Show all 15Show fewer
- Ability to comply with study procedures in the Investigator's opinion
- Aged 18 years or over
- ECOG performance status 0 or 1
- Predicted life expectancy of ≥6 months
- Adequate lung reserve
- Adequate renal function
- Adequate hepatic function
- Adequate bone marrow function
- Meeting reproductive status requirements
Who cannot join
- Prior or planned allogeneic or autologous bone marrow or organ transplantation
- Splenectomy
- Active infections requiring antibiotics, physician monitoring or systemic therapy within 1 week of the anticipated first dose of study drug, or recurrent fevers (>38.0˚C) associated with a clinical diagnosis of active infection
- Treatment with the antiviral agents: ribavirin, adefovir, lamivudine, cidofovir or paxlovid 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
- Known history of hepatitis B infection or known active hepatitis C infection . Known history of HIV infection
- Patients who have active, known or suspected autoimmune disease that has required systemic therapy in the past 2 years, are immunocompromised in the opinion of the Investigator, or are receiving long-term systemic immunosuppressive treatment
Show all 34Show fewer
- Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before the first dose of NG-641 or nivolumab
- Treatment with any other vaccine (including known non-live/live-attenuated and non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641
- History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
- History of clinically significant interstitial lung disease or non-infectious pneumonitis
- Lymphangitic carcinomatosis
- Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
- Any known CTCAE Grade ≥2 coagulation abnormality/coagulopathy
- Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or thromboembolic event in the 6 months before the first dose of study treatment
- Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding), haemoptysis, or any history of bleeding requiring an investigative procedure, transfusion or hospitalisation in the 6 months before the first dose of study treatment
- Tumour location/extent considered by the Investigator to present a significant risk if tumour flare or necrosis were to occur
- Known retinopathy, including retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy and retinal artery or vein obstruction
- Active clinically severe depression
- Use of the following prior therapies/treatments
- Treatment with any other enadenotucirev-based virus (parent virus or transgene-modified variants), or fibroblast activation protein (FAP) targeting agent at any time
- Treatment with an investigational or licensed anti-cancer monoclonal antibody (mAb), immune checkpoint inhibitor, immune stimulatory treatment, or other biological therapy in the 28 days prior to the first dose of study treatment
- Prior anti-PD-1/PD-L1 therapy is permitted without a 'washout' phase
- Treatment with an investigational or licensed chemotherapy, targeted small molecule, or other investigational drug in the 14 days or five half-lives (whichever is shorter) before the first dose of study treatment
- Major surgery in the 28 days before the first dose of study treatment
- Radiation therapy in the 14 days before the first dose of study treatment
- Treatment with complementary medications to treat the disease under study within the 14 days prior to first study treatment
- Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor Kappa-Β (RANK)-ligand inhibitors for metastatic bone disease is permitted
- All toxicities attributed to prior anti-cancer therapy (including radiation therapy) must have resolved to Grade 1 or baseline before the first dose of study treatment (see protocol for exceptions)
- Known allergy or hypersensitivity (Grade ≥3) to NG-641 transgene, immune checkpoint inhibitor products or formulation, or other monoclonal antibodies
- Known hypersensitivity to both cidofovir and valacyclovir
- Discontinuation from prior treatment with an immune therapy due to a Grade ≥3 immune-related AE, or any history of life-threatening toxicity related to prior immune therapy except those that are unlikely to re-occur with standard countermeasures
- Other prior malignancy active within the previous 3 year (see protocol for exceptions)
- Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic and/or requires treatment (see protocol for exceptions)
- Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the patient to receive protocol therapy or interfere with the interpretation of study results
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States4 sites
Moffitt-Advent Health Clinical Research Unit
Celebration, Florida, 34747
University of Cincinnati Cancer Center
Cincinnati, Ohio, 45267
Providence Medical Foundation
Fullerton, California, 92835
UCLA Department of Medicine
Santa Monica, California, 90404
United Kingdom2 sites
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, Lancashire, L7 8YA
Oxford University Hospitals NHS Foundation Trust
Oxford, Oxfordshire, OX3 7LE
About this study
Official title: A Multicentre, Open-label, Non-randomized, Phase 1a/1b Study of NG-641, a Tumour-selective and Transgene-expressing Adenoviral Vector, in Combination With Nivolumab (or Standard of Care PD-1 Inhibition) in Patients With Metastatic or Advanced Epithelial Tumours (NEBULA)
This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination with nivolumab (or standard of care PD-1 inhibition) in patients with metastatic or advanced epithelial tumours.
The purpose is to characterize the safety and tolerability of NG-641 in combination with nivolumab in patients with metastatic or advanced epithelial tumours and to determine the recommended dose of NG-641 in combination with nivolumab for further development in patients with metastatic or advanced epithelial tumours
Read the detailed description
The Phase 1a part of the study is a dose escalation phase and is composed of two parts: Part A, which is investigating NG-641 administration (single cycle) by intravenous (IV) infusion in combination with up to 8 cycles of nivolumab; and Part B, which is investigating multicycle NG-641 administration (up to 8 cycles) by IV infusion in combination with up to 8 cycles of nivolumab. Both parts will include patients with metastatic or advanced tumours. Part B will open once a recommended starting dose of NG-641 is identified from the single-cycle dose escalation. Dose escalation in Part A may continue in parallel once Part B has opened.
The Phase 1b part of the study will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in phase 1b (tumour-specific Dose Expansion Cohorts A, B and C). A Simon 2-stage design will be used, with sample size calculations and futility criteria specific to each individual expansion cohort. Patients enrolled in Cohort A will have recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is considered incurable by local therapies and has been recently treated with a first-line platinum-based chemotherapy regimen or platinum-based chemotherapy plus pembrolizumab.
Patients enrolled in Cohort A will be subdivided in to two groups according to whether they have received prior anti-PD-1 therapy (Cohort A1, chemotherapy regimen without pembrolizumab; Cohort A2, chemotherapy regimen with pembrolizumab) with each sub-cohort using a separate Simon 2-stage model. Patients in Cohort A2 who are already receiving pembrolizumab as standard of care at enrolment may continue this background treatment in combination with the recommended NG-641 dose; patients are permitted to switch to nivolumab at the Investigator's discretion. Cohorts B and C will be defined in a future protocol update that will be submitted for approval prior to these cohorts opening.
Following treatment, patients will be followed every 8 weeks until 12 months from first dose for disease status, overall survival, further cancer therapy and the best response and date of disease progression on further cancer therapy. These assessments may be performed by telephone calls or at routine visits to the hospital.
- Conditions
- Metastatic Cancer, Epithelial Tumor
- Being tested
- NG-641 in combination with Nivolumab
- Keywords
- Metastatic Cancer, Epithelial Tumor, Viral vector, Advanced, PsiOxus
- Medical subject headings
- Neoplasm Metastasis, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NG-641 in combination with NivolumabBiological
NG-641 is a replication competent adenoviral vector producing a bispecific T cell activator (TAc) targeting fibroblast activation protein (FAP) plus immune enhancer genes CXCL9/CXCL10/IFNa2. This can lead to killing of tumor cells and stimulation of immunity against the tumor cells.
Nivolumab is a human monoclonal antibody that targets the PD-1 cluster of differentiation 279 cell surface membrane receptor.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous | Experimental | Phase 1a Part A: One cycle (28 days) of NG-641 on Days 1, 3 and 5 and nivolumab on Day 15, followed by nivolumab every 4 weeks.
Phase 1a Part B: NG-641 on Days 1, 3 and 5 and one nivolumab on Day 15 in each of up to eight 28-day cycles. Receives: Biological: NG-641 in combination with Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (safety and tolerability) in study of NG-641 in combination with nivolumab
Incidence of: adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation of study treatment or study discontinuation and AEs resulting in death and Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria
Measured: 30 days after last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2021
- Study start1 Dec 2021
- Primary completion13 Nov 2023
- Study completion4 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akamis Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Christian Ottensmeier, MD, Principal investigator, Clatterbridge Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05043714
- Sponsor's protocol ID
- NG-641-03
- Acronym
- NEBULA
- Status last verified
- Aug 2024
- First submitted
- 2 Sep 2021
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.
PubMed 36897458
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Open-label, Non-randomized, Phase 1a/1b Study of NG-641, a Tumour-selective and Transgene-expressing Adenoviral Vector, in Combination With Nivolumab (or Standard of Care PD-1 Inhibition) in Patients With Metastatic or Advanced Epithelial Tumours (NEBULA)
- ClinicalTrials.gov ID
- NCT05043714
- Acronym / sponsor ID
- NEBULA / NG-641-03
- Conditions
- Metastatic Cancer, Epithelial Tumor
- Keywords
- Metastatic Cancer, Epithelial Tumor, Viral vector, Advanced, PsiOxus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Akamis BioIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 13 Nov 2023 (actual)
- Study completion
- 4 Oct 2024 (actual)
- First posted
- 14 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination with nivolumab (or standard of care PD-1 inhibition) in patients with metastatic or advanced epithelial tumours.
The purpose is to characterize the safety and tolerability of NG-641 in combination with nivolumab in patients with metastatic or advanced epithelial tumours and to determine the recommended dose of NG-641 in combination with nivolumab for further development in patients with metastatic or advanced epithelial tumours
Detailed description
The Phase 1a part of the study is a dose escalation phase and is composed of two parts: Part A, which is investigating NG-641 administration (single cycle) by intravenous (IV) infusion in combination with up to 8 cycles of nivolumab; and Part B, which is investigating multicycle NG-641 administration (up to 8 cycles) by IV infusion in combination with up to 8 cycles of nivolumab. Both parts will include patients with metastatic or advanced tumours. Part B will open once a recommended starting dose of NG-641 is identified from the single-cycle dose escalation. Dose escalation in Part A may continue in parallel once Part B has opened.
The Phase 1b part of the study will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in phase 1b (tumour-specific Dose Expansion Cohorts A, B and C). A Simon 2-stage design will be used, with sample size calculations and futility criteria specific to each individual expansion cohort. Patients enrolled in Cohort A will have recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is considered incurable by local therapies and has been recently treated with a first-line platinum-based chemotherapy regimen or platinum-based chemotherapy plus pembrolizumab.
Patients enrolled in Cohort A will be subdivided in to two groups according to whether they have received prior anti-PD-1 therapy (Cohort A1, chemotherapy regimen without pembrolizumab; Cohort A2, chemotherapy regimen with pembrolizumab) with each sub-cohort using a separate Simon 2-stage model. Patients in Cohort A2 who are already receiving pembrolizumab as standard of care at enrolment may continue this background treatment in combination with the recommended NG-641 dose; patients are permitted to switch to nivolumab at the Investigator's discretion. Cohorts B and C will be defined in a future protocol update that will be submitted for approval prior to these cohorts opening.
Following treatment, patients will be followed every 8 weeks until 12 months from first dose for disease status, overall survival, further cancer therapy and the best response and date of disease progression on further cancer therapy. These assessments may be performed by telephone calls or at routine visits to the hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous | Experimental | Biological: NG-641 in combination with NivolumabPhase 1a Part A: One cycle (28 days) of NG-641 on Days 1, 3 and 5 and nivolumab on Day 15, followed by nivolumab every 4 weeks. Phase 1a Part B: NG-641 on Days 1, 3 and 5 and one nivolumab on Day 15 in each of up to eight 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically or cytologically documented metastatic/advanced epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.
- At least one measurable site of disease according to RECIST Version 1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area
- Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
- Provide written informed consent to participate
- Ability to comply with study procedures in the Investigator's opinion
Key exclusion criteria (34 listed)
- Prior or planned allogeneic or autologous bone marrow or organ transplantation
- Splenectomy
- Active infections requiring antibiotics, physician monitoring or systemic therapy within 1 week of the anticipated first dose of study drug, or recurrent fevers (>38.0˚C) associated with a clinical diagnosis of active infection
- Treatment with the antiviral agents: ribavirin, adefovir, lamivudine, cidofovir or paxlovid 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
- Known history of hepatitis B infection or known active hepatitis C infection . Known history of HIV infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NG-641 in combination with NivolumabNG-641 is a replication competent adenoviral vector producing a bispecific T cell activator (TAc) targeting fibroblast activation protein (FAP) plus immune enhancer genes CXCL9/CXCL10/IFNa2. This can lead to killing of tumor cells and stimulation of immunity against the tumor cells. Nivolumab is a human monoclonal antibody that targets the PD-1 cluster of differentiation 279 cell surface membrane receptor. | Biological | Intravenous |
Primary outcome
Incidence of adverse events (safety and tolerability) in study of NG-641 in combination with nivolumab
Time frame: 30 days after last dose of study drug
Incidence of: adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation of study treatment or study discontinuation and AEs resulting in death and Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Derived from this study: PubMed 36897458Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Ottensmeier, MD principal investigator
Clatterbridge Cancer Centre
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NG-641 in combination with Nivolumab in people with Metastatic Cancer and Epithelial Tumor, run by Akamis Bio at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (safety and tolerability) in study of NG-641 in combination with nivolumab (time frame: 30 days after last dose of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05043714, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.